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Li DL, Ma LL, Guan ZA, Zhao YX, Jiang C. Establishment and validation of a clinical prediction model for colorectal adenoma risk factors. Oncol Lett 2025; 30:322. [PMID: 40370646 PMCID: PMC12076052 DOI: 10.3892/ol.2025.15068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 04/01/2025] [Indexed: 05/16/2025] Open
Abstract
Colorectal adenomas are benign tumors of the colorectal mucosal epithelium that have malignant potential and are regarded as precancerous lesions of colorectal cancer, for which the specific risk factors are unclear. The present study aimed to identify independent risk factors for colorectal adenoma to develop a prediction model and test its predictive value. A retrospective analysis was performed using data from patients who underwent electronic colonoscopy at the Department of Proctology (Affiliated Hospital of Shandong University of Traditional Chinese Medicine; Jinan, China) from January 2013 to December 2023 and had polyps removed during colonoscopy. Patients with colorectal adenoma were included in the case group, whilst those with no visible abnormalities on endoscopy or with non-adenomatous polyps were included as a control group. The patients were randomly divided into a training and validation group in a 7:3 ratio. Variables were screened using single-component analysis and the filtered variables were employed in multivariate logistic regression to create a clinical prediction model. Finally, the model was internally and externally validated. A total of 730 patients were included in the present study, with 286 assigned to the case group and 444 to the control group. After the initial screening of 39 variables, 12 continued to the next round, resulting in four potential predictors including age, daily number of bowel movements, thrombin time and the number of polyps. A prediction model was created based on these variables. Regarding internal validation, the C-index was 0.7054 [95% confidence interval (CI), 0.6596-0.7512] and the prediction probability in the calibration curve was close to the diagonal line of the calibration graph, indicating that the prediction probability of the model was reasonable. Regarding external validation, the C-index in the validation cohort was 0.6306 (95% CI, 0.5560-0.7053) and the calibration curve also demonstrated good identification capabilities. The Hosmer-Lemeshow test revealed that the model had a reasonable calibration degree, with χ2=9.7893, degree of freedom=8 and P=0.28. The receiver operating characteristic curve and decision curve analysis for the training and validation cohorts demonstrated good efficacy and an ideal application value. In conclusion, the model constructed in the present study demonstrated moderate predictive accuracy for colorectal adenoma risk, laying the groundwork for early detection of colorectal adenoma and secondary prevention of colorectal cancer.
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Affiliation(s)
- Dong-Lin Li
- The First College of Clinical Medicine, Shandong Traditional Chinese Medicine University, Jinan, Shandong 250000, P.R. China
| | - Ling-Ling Ma
- Department of Gastroenterology, Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong 257091, P.R. China
| | - Zhong-An Guan
- Department of Proctology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, P.R. China
| | - Yu-Xin Zhao
- The First College of Clinical Medicine, Shandong Traditional Chinese Medicine University, Jinan, Shandong 250000, P.R. China
| | - Chuan Jiang
- Department of Proctology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, P.R. China
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Wang T, Shen Z, Yang L, Zhang X, Yu M, Yu S, Zhao B. The coagulation and tumor system are directly linked through the proteolysis and activation of epidermal growth factor receptor by thrombin. Oncogene 2025; 44:1153-1166. [PMID: 39910317 DOI: 10.1038/s41388-025-03296-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 01/10/2025] [Accepted: 01/30/2025] [Indexed: 02/07/2025]
Abstract
Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer. Unfortunately, this knowledge has not yet led to any breakthrough in cancer therapy. Thrombin is the key enzyme of blood coagulation system. The identification of a direct link between thrombin and the tumor progression remains unknown. We illustrated thrombin expression in lung adenocarcinoma (LUAD) was closely related to clinicopathological features, prognosis, and chemotherapy outcome of patients via TCGA and clinical pathological analysis. Using genetic and pharmacological approaches, we showed a direct link between thrombin catalytic activity and lung cancer progression in vitro and in vivo. Furthermore, we revealed that thrombin cleaves epidermal growth factor receptor (EGFR) at a GRG motif perfectly conserved across disparate species, indicating functional importance, which results in activation of EGFR/AKT/mTOR signaling pathway. Last we found the mutual interaction between thrombin and chemotherapy resistance. Combination therapy of thrombin inhibitor and chemotherapy results in improved anti-tumor efficacy. Together, our data firstly revealed a mechanism of cancer progression and chemotherapy resistance that involves thrombin-mediated EGFR cleavage. We propose that thrombin could be a prognostic biomarker for lung cancer, blockade of thrombin is a valuable therapeutic strategy to overcome cancer's resistance to chemotherapy.
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Affiliation(s)
- Tianfa Wang
- Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Zhiyuan Shen
- Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Liu Yang
- Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xiaohan Zhang
- Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Min Yu
- Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
- Qidong-Fudan Innovative Institute of Medical Sciences, Nantong, Jiangsu Province, China.
| | - Sanjian Yu
- Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Bing Zhao
- Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
- Qidong-Fudan Innovative Institute of Medical Sciences, Nantong, Jiangsu Province, China.
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Song K, Chen C, Xu H, Chen L, Xu H, Han X, Chen H, Qin Z. Prediction of Survival in the Elderly Patients with Glioblastoma using Cumulative Inflammatory Markers Score. J Neurol Surg B Skull Base 2025; 86:98-105. [PMID: 39881741 PMCID: PMC11774615 DOI: 10.1055/s-0044-1779050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 12/21/2023] [Indexed: 01/31/2025] Open
Abstract
Objectives This retrospective study aimed to explore the prognostic effect of cumulative score based on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and fibrinogen in older adults diagnosed with glioblastoma (GBM). Design Retrospective study. Setting Huashan Hospital. Participants Patients aged over 60 years and diagnosed with GBM between 2010 and 2017. Main Outcome Measures Results of preoperative routine biochemistry and coagulation blood examinations were reviewed from medical records. Overall survival (OS) was considered a period from first resection surgery until death. Progression-free survival (PFS) was considered a period from initial operation until the date of tumor progression demonstrated in brain magnetic resonance imaging or death from any cause. If no event occurred, the last follow-up appointment was the end of the observation for OS or PFS. The Kaplan-Meier method was used to evaluate survival curves, and prognostic factors were analyzed by the Cox proportional hazards model. Results A total of 289 patients were included. Patients with higher levels of fibrinogen, NLR, and PLR had significantly shorter median OS ( p = 0.001, p = 0.016, and p = 0.002, respectively) and PFS ( p = 0.004, p = 0.022, and p = 0.009, respectively) compared with those with lower levels. Multivariate analyses showed a significant association between higher F-NLR-PLR score and reduced OS (adjusted hazard ratios [aHRs]: 1.356, 95% confidence interval [CI] 1.009-1.822 for scores 1-2 compared with 0; 5.974, 95% CI 2.811-12.698 for score 3 compared with 0). Similarly, a significant association between higher F-NLR-PLR score and reduced PFS was observed (aHR: 1.428, 95% CI 1.066-1.912 for scores 1-2 compared with 0; aHR: 2.860, 95% CI 1.315-6.223 for score 3 compared with 0). Conclusion Higher F-NLR-PLR score is associated with reduced OS and PFS in older adults with GBM, which helps identify patients at high risk and guide the individualized treatment in clinical practice.
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Affiliation(s)
- Kun Song
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Chunjui Chen
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Hao Xu
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Lingchao Chen
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Hongzhi Xu
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Xi Han
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Hong Chen
- Department of Neuropathology, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiyong Qin
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
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Tang B, Wu F, Peng L, Leng X, Han Y, Wang Q, Wu J, Orlandini LC. Computed tomography-based radiomics nomogram for prediction of lympho-vascular and perineural invasion in esophageal squamous cell cancer patients: a retrospective cohort study. Cancer Imaging 2024; 24:131. [PMID: 39367492 PMCID: PMC11451056 DOI: 10.1186/s40644-024-00781-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 09/30/2024] [Indexed: 10/06/2024] Open
Abstract
PURPOSE Lympho-vascular invasion (LVI) and perineural invasion (PNI) have been established as prognostic factors in various types of cancers. The preoperative prediction of LVI and PNI has the potential to guide personalized medicine strategies for patients with esophageal squamous cell cancer (ESCC). This study investigates whether radiomics features derived from preoperative contrast-enhanced CT could predict LVI and PNI in ESCC patients. METHODS AND MATERIALS A retrospective cohort of 544 ESCC patients who underwent esophagectomy were included in this study. Preoperative contrast-enhanced CT images, pathological results of PNI and LVI, and clinical characteristics were collected. For each patient, the gross tumor volume (GTV-T) and lymph nodes volume (GTV-N) were delineated and four categories of radiomics features (first-order, shape, textural and wavelet) were extracted from GTV-T and GTV-N. The Mann-Whitney U test was used to select significant features associated with LVI and PNI in turn. Subsequently, radiomics signatures for LVI and PNI were constructed using LASSO regression with ten-fold cross-validation. Significant clinical characteristics were combined with radiomics signature to develop two nomogram models for predicting LVI and PNI, respectively. The area under the curve (AUC) and calibration curve were used to evaluate the predictive performance of the models. RESULTS The radiomics signature for LVI prediction consisted of 28 features, while the PNI radiomics signature comprised 14 features. The AUCs of the LVI radiomics signature were 0.77 and 0.74 in the training and validation groups, respectively, while the AUCs of the PNI radiomics signature were 0.69 and 0.68 in the training and validation groups. The nomograms incorporating radiomics signatures and significant clinical characteristics such as age, gender, thrombin time and D-Dimer showed improved predictive performance for both LVI (AUC: 0.82 and 0.80 in the training and validation group) and PNI (AUC: 0.75 and 0.72 in the training and validation groups) compared to the radiomics signature alone. CONCLUSION The radiomics features extracted from preoperative contrast-enhanced CT of gross tumor and lymph nodes have demonstrated their potential in predicting LVI and PNI in ESCC patients. Furthermore, the incorporation of clinical characteristics has shown additional value, resulting in improved predictive performance.
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Affiliation(s)
- Bin Tang
- Department of Radiation Oncology, Radiation Onocology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Fan Wu
- Department of Radiation Oncology, Radiation Onocology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Lin Peng
- Department of Thoracic Surgery, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Xuefeng Leng
- Department of Thoracic Surgery, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Yongtao Han
- Department of Thoracic Surgery, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
| | - Qifeng Wang
- Department of Radiation Oncology, Radiation Onocology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
| | - Junxiang Wu
- Department of Radiation Oncology, Radiation Onocology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China.
| | - Lucia Clara Orlandini
- Department of Radiation Oncology, Radiation Onocology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, China
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Urbiola-Salvador V, Jabłońska A, Miroszewska D, Kamysz W, Duzowska K, Drężek-Chyła K, Baber R, Thieme R, Gockel I, Zdrenka M, Śrutek E, Szylberg Ł, Jankowski M, Bała D, Zegarski W, Nowikiewicz T, Makarewicz W, Adamczyk A, Ambicka A, Przewoźnik M, Harazin-Lechowska A, Ryś J, Macur K, Czaplewska P, Filipowicz N, Piotrowski A, Dumanski JP, Chen Z. Mass Spectrometry Proteomics Characterization of Plasma Biomarkers for Colorectal Cancer Associated With Inflammation. Biomark Insights 2024; 19:11772719241257739. [PMID: 38911905 PMCID: PMC11191626 DOI: 10.1177/11772719241257739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 05/07/2024] [Indexed: 06/25/2024] Open
Abstract
Background Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed. Objective and design This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers. Results Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages. Conclusion Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
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Affiliation(s)
- Víctor Urbiola-Salvador
- Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Agnieszka Jabłońska
- Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Dominika Miroszewska
- Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Weronika Kamysz
- Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Katarzyna Duzowska
- 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Kinga Drężek-Chyła
- 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Ronny Baber
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Universitätsklinikum Leipzig, Leipzig University, Leipzig, Saxony, Germany
- Leipzig Medical Biobank, Leipzig University, Leipzig, Saxony, Germany
| | - René Thieme
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Saxony, Germany
| | - Ines Gockel
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Saxony, Germany
| | - Marek Zdrenka
- Department of Tumor Pathology and Pathomorphology, Oncology Center‒Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Kuyavian-Pomeranian, Poland
| | - Ewa Śrutek
- Department of Tumor Pathology and Pathomorphology, Oncology Center‒Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Kuyavian-Pomeranian, Poland
| | - Łukasz Szylberg
- Department of Tumor Pathology and Pathomorphology, Oncology Center‒Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Kuyavian-Pomeranian, Poland
- Department of Obstetrics, Gynaecology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Kuyavian-Pomeranian, Poland
| | - Michał Jankowski
- Surgical Oncology, Ludwik Rydygier’s Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Kuyavian-Pomeranian, Poland
- Department of Surgical Oncology, Oncology Center‒Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Kuyavian-Pomeranian, Poland
| | - Dariusz Bała
- Surgical Oncology, Ludwik Rydygier’s Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Kuyavian-Pomeranian, Poland
- Department of Surgical Oncology, Oncology Center‒Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Kuyavian-Pomeranian, Poland
| | - Wojciech Zegarski
- Surgical Oncology, Ludwik Rydygier’s Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Kuyavian-Pomeranian, Poland
- Department of Surgical Oncology, Oncology Center‒Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Kuyavian-Pomeranian, Poland
| | - Tomasz Nowikiewicz
- Surgical Oncology, Ludwik Rydygier’s Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Kuyavian-Pomeranian, Poland
- Department of Breast Cancer and Reconstructive Surgery, Oncology Center‒Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Kuyavian-Pomeranian, Poland
| | - Wojciech Makarewicz
- Clinic of General and Oncological Surgery, Specialist Hospital of Kościerzyna, Kościerzyna, Pomeranian, Poland
| | - Agnieszka Adamczyk
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Lesser Poland, Poland
| | - Aleksandra Ambicka
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Lesser Poland, Poland
| | - Marcin Przewoźnik
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Lesser Poland, Poland
| | - Agnieszka Harazin-Lechowska
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Lesser Poland, Poland
| | - Janusz Ryś
- Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Lesser Poland, Poland
| | - Katarzyna Macur
- Laboratory of Mass Spectrometry-Core Facility Laboratories, Intercollegiate Faculty of Biotechnology University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Paulina Czaplewska
- Laboratory of Mass Spectrometry-Core Facility Laboratories, Intercollegiate Faculty of Biotechnology University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Natalia Filipowicz
- 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Arkadiusz Piotrowski
- 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Jan P Dumanski
- 3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Pomeranian, Poland
- Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Uppland, Sweden
- Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, Gdańsk, Pomeranian, Poland
| | - Zhi Chen
- Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, University of Gdańsk, Gdańsk, Pomeranian, Poland
- Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, North Ostrobothnia, Finland
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Han Y, Ren Z, Liu Y, Liu Y. Diagnostic and Prognostic Value of Fibrinogen, Fibrinogen Degradation Products, and Lymphocyte/Monocyte Ratio in Patients With Laryngeal Squamous Cell Carcinoma. EAR, NOSE & THROAT JOURNAL 2024; 103:NP278-NP288. [PMID: 34672822 DOI: 10.1177/01455613211048970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
OBJECTIVES Laryngeal squamous cell carcinoma (LSCC) is a common squamous cell carcinoma of the head and neck with no reliable diagnostic biomarkers. However, recent studies have shown that inflammation plays an essential role in tumor development, and several inflammation-based biomarkers have been shown to have prognostic value. This study aimed to investigate the auxiliary value of fibrinogen (FIB), fibrinogen degradation products (FDP), and lymphocyte/monocyte ratio (LMR) in LSCC diagnosis and prognosis. METHODS Clinical data from 218 patients recently diagnosed with LSCC and 207 diagnosed with benign laryngeal lesions (BLLs) were retrospectively reviewed. Potential diagnostic biomarkers were evaluated using univariate and multivariate analyses; receiver operating characteristic (ROC) curve analysis was used to identify cut-off values and diagnostic efficiency. Least absolute shrinkage and selection operator (LASSO) Logistic regression analysis was used to screen for independent risk factors to construct a diagnostic nomogram. The chi-squared test and Kaplan-Meier method were performed to investigate the correlation of clinicopathological characteristics and 3-year overall survival (OS) with FIB, FDP, and LMR in patients with LSCC. RESULTS FIB, FDP, and LMR levels were significantly different between the LSCC and BLL groups (P < .001), and all were independent risk factors for LSCC. The area under the ROC curve of the diagnostic nomogram was .894. Additionally, FIB, FDP, and LMR were correlated with some invasive clinicopathological features, and LMR ≥4.29 was associated with reduced OS (P = .038). CONCLUSION FIB, FDP, and LMR demonstrated potential as biomarkers for the diagnosis and prognosis of LSCC; however, further studies are needed to confirm their efficacy.
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Affiliation(s)
- Yanxun Han
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhiyao Ren
- Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yuchen Liu
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yehai Liu
- Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Zhang X, Qiu X, Yin H, Zhao W, Song L, Zhang X, Yang L, Tao M. The combination of preoperative fibrinogen-to-albumin ratio and postoperative TNM stage (FAR-TNM) predicts the survival in gastric cancer patients after gastrectomy. Biomarkers 2023; 28:714-721. [PMID: 38059615 DOI: 10.1080/1354750x.2023.2281870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 11/05/2023] [Indexed: 12/08/2023]
Abstract
OBJECTIVE There are many factors that affect the survival of patients with gastric cancer, such as TNM stage, the patient's nutritional status, inflammation, and so on. In this study, the prognostic significance of preoperative fibrinogen-to-albumin ratio (FAR) and postoperative TNM staging in patients with gastric cancer was retrospectively studied. METHODS A total of 265 patients (surgery dates from January 2007 to December 2013) were included in this retrospective study. All the patients were confirmed by pathology after operation. Categorical variables were compared using the χ2 test. Kaplan-Meier and log-rank tests were used for survival analysis. Cox proportional hazard models were used to assess prognostic factors. Nomogram was applied to predict the prognosis of overall survival (OS). RESULTS The higher the FAR value, the more lymph node metastasis, the later the TNM stage, and the shorter the survival time. We established a new scoring system, the FAR-TNM score, which combined FAR and TNM stage. The FAR-TNM score was significantly related to tumor location, tumor size, Bormann types, differentiation, operative type, vascular invasion, nerve invasion, depth of invasion, lymphatic metastasis, and advanced TNM stage. Multivariate Cox regression analysis demonstrated that tumor location, TNM stage, adjuvant chemotherapy, and FAR-TNM score were independent prognostic elements for OS in patients with GC. CONCLUSIONS The FAR-TNM score was a valuable independent prognostic indicator for GC patients after surgery, which can help clinicians to assist the treatment and long-term management of patients with gastric cancer.
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Affiliation(s)
- Xunlei Zhang
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China
| | - Xinyue Qiu
- Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China
| | - Haibing Yin
- Department of Pathology, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China
| | - Wenjing Zhao
- Cancer Research Center, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China
| | - Li Song
- Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China
| | - Xingsong Zhang
- Department of Pathology, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China
| | - Lei Yang
- Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu, China
| | - Min Tao
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
- Department of Oncology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
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Plahuta I, Mencinger M, Peruš I, Magdalenić T, Turk Š, Brumec A, Potrč S, Ivanecz A. Ranking as a Procedure for Selecting a Replacement Variable in the Score Predicting the Survival of Patients Treated with Curative Intent for Colorectal Liver Metastases. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2003. [PMID: 38004052 PMCID: PMC10673064 DOI: 10.3390/medicina59112003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/04/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023]
Abstract
Background and Objectives: The issue of a missing variable precludes the external validation of many prognostic models. For example, the Liverpool score predicts the survival of patients undergoing surgical therapy for colorectal liver metastases, but it includes the neutrophil-lymphocyte ratio, which cannot be measured retrospectively. Materials and Methods: We aimed to find the most appropriate replacement for the neutrophil-lymphocyte ratio. Survival analysis was performed on data representing 632 liver resections for colorectal liver metastases from 2000 to 2020. Variables associated with the Liverpool score, C-reactive protein, albumins, and fibrinogen were ranked. The rankings were performed in four ways: The first two were based on the Kaplan-Meier method (log-rank statistics and the definite integral IS between two survival curves). The next method of ranking was based on univariate and multivariate Cox regression analyses. Results: The ranks were as follows: the radicality of liver resection (rank 1), lymph node infiltration of primary colorectal cancer (rank 2), elevated C-reactive protein (rank 3), the American Society of Anesthesiologists Classification grade (rank 4), the right-sidedness of primary colorectal cancer (rank 5), the multiplicity of colorectal liver metastases (rank 6), the size of colorectal liver metastases (rank 7), albumins (rank 8), and fibrinogen (rank 9). Conclusions: The ranking methodologies resulted in almost the same ranking order of the variables. Elevated C-reactive protein was ranked highly and can be considered a relevant replacement for the neutrophil-lymphocyte ratio in the Liverpool score. These methods are suitable for ranking variables in similar models for medical research.
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Affiliation(s)
- Irena Plahuta
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
| | - Matej Mencinger
- Faculty of Civil Engineering, Transportation Engineering, and Architecture, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia; (M.M.); (I.P.)
- Institute of Mathematics, Physics and Mechanics, Jadranska 19, 1000 Ljubljana, Slovenia
| | - Iztok Peruš
- Faculty of Civil Engineering, Transportation Engineering, and Architecture, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia; (M.M.); (I.P.)
- Faculty of Natural Science and Engineering, University of Ljubljana, Aškerčeva cesta 12, 1000 Ljubljana, Slovenia
| | - Tomislav Magdalenić
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Špela Turk
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Aleks Brumec
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Stojan Potrč
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
| | - Arpad Ivanecz
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
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9
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Shen Y, Li Y, Wang Z, Xu W, Wang W, Chen X. The prognostic value of FAR and a novel FAR-CA125 score in resectable gastric signet ring cell carcinoma patients. J Cancer Res Clin Oncol 2023; 149:9597-9608. [PMID: 37222811 DOI: 10.1007/s00432-023-04870-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 05/19/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND The fibrinogen to albumin ratio (FAR) is increasingly regarded as a potential biomarker for predicting prognosis in variety of malignant tumors, but not in gastric signet ring cell carcinoma (GSRC). This study seeks to examine the prognostic value of the FAR and explore a novel FAR-CA125 score (FCS) in resectable GSRC patients. METHODS A retrospective cohort was conducted including 330 GSRC patients who underwent curative resection. Kaplan-Meier (K-M) and Cox regression were used to analysis the prognostic value of FAR and FCS. And a predictive nomogram model was developed. RESULTS The optimal cut-off values for CA125 and FAR were 9.88 and 0.0697, respectively, according to the receiver operating characteristic curve (ROC). Th area under the ROC curve of FCS is higher than CA125 and FAR. 330 patients were grouped into three groups according to the FCS. High FCS was related to males, anemia, tumor size, TNM stage, lymph node metastasis, tumor invasion depth, SII, and pathological subtypes. K-M analysis showed that high FCS and FAR were associated with poor survival. In the multivariate analysis, FCS, TNM stage, and SII were independent prognostic factors for poor OS in resectable GSRC patients. And the predictive accuracy of clinical nomogram contained FCS was better than TNM stage. CONCLUSION This study indicated that the FCS is a prognostic, and effective biomarker for patients with surgically resectable GSRC. Such developed FCS-based nomogram could be effective tools to assist the clinicians to determine the treatment strategy.
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Affiliation(s)
- Yimin Shen
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Yuanyuan Li
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Zhou Wang
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Wei Xu
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu, China
| | - Wenjie Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China
| | - Xiao Chen
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China.
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Wang Y, Schneider SW, Gorzelanny C. Crosstalk between Circulating Tumor Cells and Plasma Proteins-Impact on Coagulation and Anticoagulation. Cancers (Basel) 2023; 15:cancers15113025. [PMID: 37296987 DOI: 10.3390/cancers15113025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/24/2023] [Accepted: 05/31/2023] [Indexed: 06/12/2023] Open
Abstract
Cancer metastasis is a complex process. After their intravasation into the circulation, the cancer cells are exposed to a harsh environment of physical and biochemical hazards. Whether circulating tumor cells (CTCs) survive and escape from blood flow defines their ability to metastasize. CTCs sense their environment with surface-exposed receptors. The recognition of corresponding ligands, e.g., fibrinogen, by integrins can induce intracellular signaling processes driving CTCs' survival. Other receptors, such as tissue factor (TF), enable CTCs to induce coagulation. Cancer-associated thrombosis (CAT) is adversely connected to patients' outcome. However, cancer cells have also the ability to inhibit coagulation, e.g., through expressing thrombomodulin (TM) or heparan sulfate (HS), an activator of antithrombin (AT). To that extent, individual CTCs can interact with plasma proteins, and whether these interactions are connected to metastasis or clinical symptoms such as CAT is largely unknown. In the present review, we discuss the biological and clinical relevance of cancer-cell-expressed surface molecules and their interaction with plasma proteins. We aim to encourage future research to expand our knowledge of the CTC interactome, as this may not only yield new molecular markers improving liquid-biopsy-based diagnostics but also additional targets for better cancer therapies.
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Affiliation(s)
- Yuanyuan Wang
- Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
| | - Stefan W Schneider
- Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
| | - Christian Gorzelanny
- Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
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11
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Wang K, Ma L, Chen L, Jiang Y, Liu N, Cai J, Zhang Y. The clinical value of a nomogram constructed from CEA, CA199, PT, FIB, tumor differentiation and TNM stage in colorectal cancer. Cancer Biomark 2023; 38:537-549. [PMID: 37980649 DOI: 10.3233/cbm-230116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2023]
Abstract
BACKGROUND The accurate Tumor-Node-Metastasis (TNM) staging of colorectal cancer (CRC) is of great guiding significance for the judgment of tumor progression and prognosis, and the formulation of treatment strategies. OBJECTIVE The aim of this study was to construct a recurrence risk scoring (RRS) system and prognostic prediction model to improve the accuracy of staging, prognosis prediction, and clinical decision making in resectable CRC. METHODS CRC patients who underwent radical resection were retrospectively enrolled into study. Multivariable Cox regression model was applied to screen for independent prognostic factors. The RRS system is composed of independent prognostic factors which was awarded 1point each. A prognostic model composed of RRS and TNM staging system (RRS-TNM model) was applied to predict postoperative recurrence. RESULTS TNM stage, tumor differentiation, preoperative elevated Carcinoembryonic Antigen, Carbohydrate Antigen 199, Prothrombin Time and Fibrinogen were the independent prognostic biomarkers. 173 of 540 patients had recurrence. The 5-year cumulative recurrence rate (5-y CRR) and disease-free survival (DFS) of postoperative p-TNM stage I, II, and III were 12.7% and 104.8 months, 26.5% and 89.3 months, and 55.5% and 57.3 months, respectively. The 5-y CRR and DFS of preoperative Low-risk (RRS 0-1score), Middle-risk (RRS 2-3scores), and High-risk (RRS 4-5scores) groups were 13.9% and 101.1 months, 40.9% and 75.5 months, and 70.2% and 41.1 months. The AUC (area under ROC curve) of RRS system was not inferior to that of TNM staging system (0.713 vs. 0.666; P= 0.093). The AUC (0.770) and C-index value (0.721) of RRS-TNM model were significantly better than both RRS and TNM staging system (P< 0.001). CONCLUSIONS The RRS system accurately identifies CRC patients with high-risk recurrence preoperatively. Constructing a nomogram using the RRS system and TNM staging significantly improves the accuracy of staging and prognosis prediction, which is of great clinical significance for individualized clinical treatment and follow-up of CRC.
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Affiliation(s)
- Kang Wang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Lulu Ma
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Liying Chen
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Yatong Jiang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Ningquan Liu
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Jianchun Cai
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Yiyao Zhang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
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Li B, Deng H, Lei B, Chen L, Zhang X, Sha D. The prognostic value of fibrinogen to albumin ratio in malignant tumor patients: A meta-analysis. Front Oncol 2022; 12:985377. [PMID: 36249067 PMCID: PMC9556778 DOI: 10.3389/fonc.2022.985377] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 09/12/2022] [Indexed: 12/24/2022] Open
Abstract
BackgroundRecent studies have shown that the fibrinogen to albumin ratio (FAR) is closely related to the prognosis of various cancers. The aim of this systematic review and meta-analysis was to investigate the prognostic value of FAR in malignancies based on the available evidence.MethodTo systematically search the Cochrane Library, Embase, PubMed, Google Scholar, Baidu scholars, CNKI and VIP databases for relevant studies published before April 1, 2022, and to evaluate the fibrinogen-to-albumin ratio (FAR) and survival of patients with malignant tumors through a meta-analysis relationship between the results. Results. This meta-analysis included 19 eligible studies involving 5926 cancer patients. We found that high FAR was associated with poor overall survival (HR=2.25, 95%CI 1.86-2.74, p<0.001), recurrence-free survival (HR=2.29, 95%CI 1.91-2.76, P<0.001), progression-free survival (HR: 2.10, 95%CI 1.58-2.79, p<0.001), disease-free survival (HR=1.52, 95%CI 1.17-1.96, p=0.001), and time to recurrence (HR: 1.555, 95%CI 1.031-2.346, P=0.035) was significantly correlated.ConclusionsHigh FAR is significantly associated with poor clinical outcomes in cancer, suggesting that it may be an important predictor of prognosis in patients with malignancies.
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Affiliation(s)
- Baibei Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Huachu Deng
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Biao Lei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Leijie Chen
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xinyuan Zhang
- The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Dingran Sha
- Department of Urology Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- *Correspondence: Dingran Sha,
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Thrombin Generation and D-Dimer for Prediction of Disease Progression and Mortality in Patients with Metastatic Gastrointestinal Cancer. Cancers (Basel) 2022; 14:cancers14184347. [PMID: 36139507 PMCID: PMC9496981 DOI: 10.3390/cancers14184347] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/31/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022] Open
Abstract
Background: the tight and reciprocal interaction between cancer and hemostasis has stimulated investigations on the possible role of hemostatic biomarkers in predicting specific cancer outcomes, such as disease progression (DP) and overall survival (OS). In a prospective cohort of newly diagnosed metastatic gastrointestinal (GI) cancer patients from the HYPERCAN study, we aimed to assess whether the hemostatic biomarker levels measured before starting any anticancer therapy may specifically predict for 6-months DP (6m-DP) and for 1-year OS (1y OS). Methods: plasma samples were collected and tested for thrombin generation (TG) as global hemostatic assay, and for D-dimer, fibrinogen, and prothrombin fragment 1 + 2 as hypercoagulation biomarkers. DP and mortality were monitored during follow-up. Results: A prospective cohort of 462 colorectal and 164 gastric cancer patients was available for analysis. After 6 months, DP occurred in 148 patients, providing a cumulative incidence of 24.8% (21.4−28.4). D-dimer and TG endogenous thrombin potential (ETP) were identified as independent risk factors for 6m-DP by multivariate Fine−Gray proportional hazard regression model corrected for age, cancer site, and >1 metastatic site. After 1 year, we observed an OS of 75.7% (71.9−79.0). Multivariate Cox regression analysis corrected for age, site of cancer, and performance status identified D-dimer and ETP as independent risk factors for 1y OS. Patients with one or both hemostatic parameters above the dichotomizing threshold were at higher risk for both 6m-DP and 1-year mortality. Conclusion.: in newly diagnosed metastatic GI cancer patients, pretreatment ETP and D-dimer appear promising candidate biomarkers for predicting 6m-DP and 1y OS. In this setting, for the first time, the role of TG as a prognostic biomarker emerges in a large prospective cohort.
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14
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Maruyama S, Matono T, Koda M. Prevalence and Characteristics of Hepatic Hemangioma Associated with Coagulopathy and Its Predictive Risk Factors. J Clin Med 2022; 11:jcm11154347. [PMID: 35893437 PMCID: PMC9368925 DOI: 10.3390/jcm11154347] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/24/2022] [Accepted: 07/24/2022] [Indexed: 12/10/2022] Open
Abstract
Background: Knowledge of the relationships between hepatic hemangiomas and coagulopathy and the risk factors for hemangiomas is lacking. The aim of this study was to investigate the prevalence and characteristics of hepatic hemangiomas associated with coagulopathy, elucidate the causes of coagulopathy, and identify the predictive factors for hemangioma-related complications. Methods: In 281 consecutive patients with hepatic hemangiomas, we performed ultrasonography and conducted serum laboratory tests for liver function and six coagulation factors, i.e., platelets, as well as five coagulation fibrinolytic markers (prothrombin time (PT), fibrinogen, thrombin-antithrombin III complex (TAT), d-dimer, and fibrin and fibrinogen degradation products (FDP)) as indicators of coagulation disorder. Results: Among 281 patients, 56 (19.9%) had abnormal coagulation factors. Abnormal values of d-dimer were most frequently found among the six coagulation factors. The number of abnormal coagulation factors was significantly correlated with tumor size, M2BPGi, and HDL cholesterol, among which tumor size was the most significant independent predictor of the number of abnormal coagulation factors. Conclusions: The prevalence of hepatic hemangiomas associated with coagulopathy was relatively high and became more frequent with increases in tumor size. Predictive factors of hemangioma-related complications were found to be a tumor size of >5 cm in diameter and coagulopathy, especially the elevation of d-dimer.
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Affiliation(s)
- Shigeo Maruyama
- Maruyama Medical Clinic, Aioimacho 3921, Hamada 697-0034, Shimane, Japan;
| | | | - Masahiko Koda
- Hino Hospital, Nota 332, Hino 689-4504, Tottori, Japan
- Correspondence: ; Tel.: +81-859-72-0351; Fax: +81-859-72-0089
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Zaragoza-Huesca D, Nieto-Olivares A, García-Molina F, Ricote G, Montenegro S, Sánchez-Cánovas M, Garrido-Rodríguez P, Peñas-Martínez J, Vicente V, Martínez F, Lozano ML, Carmona-Bayonas A, Martínez-Martínez I. Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients. Cancers (Basel) 2022; 14:cancers14133106. [PMID: 35804878 PMCID: PMC9264764 DOI: 10.3390/cancers14133106] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/21/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022] Open
Abstract
Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical-histopathological variables by using the chi-square and Kruskal−Wallis tests, Kaplan−Meier and Aalen−Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value = 0.035 and hazard ratio 3.30, p-value = 0.012, respectively), being a better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were associated with an increase in thrombotic risk (hazard ratio 7.71, p-value = 0.043 and hazard ratio 9.02, p-value = 0.028, respectively). This relationship was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical way with respect to differentiation and invasion processes.
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Affiliation(s)
- David Zaragoza-Huesca
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
| | - Andrés Nieto-Olivares
- Department of Pathology, Hospital General Universitario Morales Meseguer, 30008 Murcia, Spain;
| | - Francisco García-Molina
- Department of Pathology, Hospital General Universitario Reina Sofía, 30003 Murcia, Spain; (F.G.-M.); (F.M.)
| | - Guillermo Ricote
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
| | - Sofía Montenegro
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
| | - Manuel Sánchez-Cánovas
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
| | - Pedro Garrido-Rodríguez
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Raras, U-765-CIBERER, Instituto de Salud Carlos III, 28220 Madrid, Spain
| | - Julia Peñas-Martínez
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
| | - Vicente Vicente
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Raras, U-765-CIBERER, Instituto de Salud Carlos III, 28220 Madrid, Spain
| | - Francisco Martínez
- Department of Pathology, Hospital General Universitario Reina Sofía, 30003 Murcia, Spain; (F.G.-M.); (F.M.)
| | - María Luisa Lozano
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Raras, U-765-CIBERER, Instituto de Salud Carlos III, 28220 Madrid, Spain
| | - Alberto Carmona-Bayonas
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
- Correspondence: (A.C.-B.); (I.M.-M.); Tel.: +34-968-341-990 (A.C.-B. & I.M.-M.)
| | - Irene Martínez-Martínez
- Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain; (D.Z.-H.); (G.R.); (S.M.); (M.S.-C.); (P.G.-R.); (J.P.-M.); (V.V.); (M.L.L.)
- Centro de Investigación Biomédica en Red de Enfermedades Raras, U-765-CIBERER, Instituto de Salud Carlos III, 28220 Madrid, Spain
- Correspondence: (A.C.-B.); (I.M.-M.); Tel.: +34-968-341-990 (A.C.-B. & I.M.-M.)
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Huang Y, Zhu Q, Xue L, Zhu X, Chen Y, Wu M. Machine Learning-Assisted Ensemble Analysis for the Prediction of Response to Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer. Front Oncol 2022; 12:817250. [PMID: 35425697 PMCID: PMC9001844 DOI: 10.3389/fonc.2022.817250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Abstract
The clinical benefit of neoadjuvant chemotherapy (NACT) before concurrent chemoradiotherapy (CCRT) vs. adjuvant chemotherapy after CCRT is debated. Non-response to platinum-based NACT is a major contributor to poor prognosis, but there is currently no reliable method for predicting the response to NACT (rNACT) in patients with locally advanced cervical cancer (LACC). In this study we developed a machine learning (ML)-assisted model to accurately predict rNACT. We retrospectively analyzed data on 636 patients diagnosed with stage IB2 to IIA2 cervical cancer at our hospital between January 1, 2010 and December 1, 2020. Five ML-assisted models were developed from candidate clinical features using 2-step estimation methods. Receiver operating characteristic curve (ROC), clinical impact curve, and decision curve analyses were performed to evaluate the robustness and clinical applicability of each model. A total of 30 candidate variables were ultimately included in the rNACT prediction model. The areas under the ROC curve of models constructed using the random forest classifier (RFC), support vector machine, eXtreme gradient boosting, artificial neural network, and decision tree ranged from 0.682 to 0.847. The RFC model had the highest predictive accuracy, which was achieved by incorporating inflammatory factors such as platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, neutrophil-to-albumin ratio, and lymphocyte-to-monocyte ratio. These results demonstrate that the ML-based prediction model developed using the RFC can be used to identify LACC patients who are likely to respond to rNACT, which can guide treatment selection and improve clinical outcomes.
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Affiliation(s)
- Yibao Huang
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qingqing Zhu
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liru Xue
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoran Zhu
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yingying Chen
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mingfu Wu
- Department of Gynecology, National Clinical Research Center for Obstetrical and Gynecological Diseases, Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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17
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Vellan CJ, Jayapalan JJ, Yoong BK, Abdul-Aziz A, Mat-Junit S, Subramanian P. Application of Proteomics in Pancreatic Ductal Adenocarcinoma Biomarker Investigations: A Review. Int J Mol Sci 2022; 23:2093. [PMID: 35216204 PMCID: PMC8879036 DOI: 10.3390/ijms23042093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/07/2022] [Accepted: 01/09/2022] [Indexed: 12/12/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignancy with a poor prognosis is usually detected at the advanced stage of the disease. The only US Food and Drug Administration-approved biomarker that is available for PDAC, CA 19-9, is most useful in monitoring treatment response among PDAC patients rather than for early detection. Moreover, when CA 19-9 is solely used for diagnostic purposes, it has only a recorded sensitivity of 79% and specificity of 82% in symptomatic individuals. Therefore, there is an urgent need to identify reliable biomarkers for diagnosis (specifically for the early diagnosis), ascertain prognosis as well as to monitor treatment response and tumour recurrence of PDAC. In recent years, proteomic technologies are growing exponentially at an accelerated rate for a wide range of applications in cancer research. In this review, we discussed the current status of biomarker research for PDAC using various proteomic technologies. This review will explore the potential perspective for understanding and identifying the unique alterations in protein expressions that could prove beneficial in discovering new robust biomarkers to detect PDAC at an early stage, ascertain prognosis of patients with the disease in addition to monitoring treatment response and tumour recurrence of patients.
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Affiliation(s)
- Christina Jane Vellan
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia; (C.J.V.); (A.A.-A.); (S.M.-J.)
| | - Jaime Jacqueline Jayapalan
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia; (C.J.V.); (A.A.-A.); (S.M.-J.)
- University of Malaya Centre for Proteomics Research (UMCPR), Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Boon-Koon Yoong
- Department of Surgery, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia;
| | - Azlina Abdul-Aziz
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia; (C.J.V.); (A.A.-A.); (S.M.-J.)
| | - Sarni Mat-Junit
- Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia; (C.J.V.); (A.A.-A.); (S.M.-J.)
| | - Perumal Subramanian
- Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram 608002, Tamil Nadu, India;
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18
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Brkic FF, Stoiber S, Friedl M, Maier T, Heiduschka G, Kadletz-Wanke L. The Potential Prognostic Value of a Novel Hematologic Marker Fibrinogen-to-Lymphocyte Ratio in Head and Neck Adenoid-Cystic Carcinoma. J Pers Med 2021; 11:jpm11111228. [PMID: 34834580 PMCID: PMC8620294 DOI: 10.3390/jpm11111228] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/09/2021] [Accepted: 11/17/2021] [Indexed: 11/16/2022] Open
Abstract
Many patients with adenoid-cystic carcinoma (ACC) experience an indolent course of disease over many years but face late recurrence, and long-term survivors are rare. Due to its infrequent occurrence, it is hard to predict outcome in these patients. The fibrinogen-to-lymphocyte ratio (FLR) was recently proposed as an outcome prognosticator in different cancer entities. We aimed to investigate its prognostic relevance in patients with head and neck ACC. This retrospective analysis was performed including all patients treated for ACC between 1998 and 2020. The FLR ratio was calculated based on pretreatment values (0-7 days). The study cohort was dichotomized based on optimized threshold value and compared for differences in outcome (overall survival (OS) and disease-free survival (DFS)). In the cohort of 39 included patients, the OS was significantly longer in the low (n = 28) compared to the high pretreatment FLR group (n = 11) (median OS 150.5 months, 95% confidence intervals (CI) 85.3-215.7 months vs. 29.4 months, 95% CI not reached; p = 0.0093). Similarly, the DFS was significantly longer in the low FLR group (median DFS 74.5 months, 95% CI 30.6-118.4 months vs. 11.0 months, 95% CI 5.1-16.9 months; p = 0.019). The FLR is an easily obtainable and simple marker and may be a valuable outcome prognosticator in patients with ACC. Further studies are needed for validation of our results.
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Affiliation(s)
- Faris F. Brkic
- Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (F.F.B.); (M.F.); (T.M.); (G.H.)
| | - Stefan Stoiber
- Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria;
- Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, 1090 Vienna, Austria
| | - Marlene Friedl
- Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (F.F.B.); (M.F.); (T.M.); (G.H.)
| | - Tobias Maier
- Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (F.F.B.); (M.F.); (T.M.); (G.H.)
| | - Gregor Heiduschka
- Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (F.F.B.); (M.F.); (T.M.); (G.H.)
| | - Lorenz Kadletz-Wanke
- Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, 1090 Vienna, Austria; (F.F.B.); (M.F.); (T.M.); (G.H.)
- Correspondence: ; Tel.: +43-1-40-400-20830
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Falanga A, Marchetti M, Russo L. Hemostatic Biomarkers and Cancer Prognosis: Where Do We Stand? Semin Thromb Hemost 2021; 47:962-971. [PMID: 34450680 DOI: 10.1055/s-0041-1733925] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Cancer patients are characterized by hypercoagulable state and an increased rate of thrombotic events, the most common being venous thromboembolism. Several hemostatic pathways that are significantly implicated in mechanisms of thromboembolic disease are also involved in growth, invasion, and metastatic spread of malignant cells as well in tumor-induced neo-angiogenesis. This close connection between cancer and the hemostatic system has prompted numerous studies on the role of alterations in the level plasma biomarkers of the different compartments of hemostasis in predicting cancer prognosis. In this review, we collect the results of several exemplificative studies that have evaluated clotting activation biomarkers in relation to different cancer outcomes with a final emphasis on current research and forthcoming directions in this field.
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Affiliation(s)
- Anna Falanga
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.,Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy
| | - Marina Marchetti
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Laura Russo
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
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20
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Izuegbuna OO, Agodirin OS, Olawumi HO, Olatoke SA. Plasma D-Dimer and Fibrinogen Levels Correlates with Tumor Size and Disease Progression in Nigerian Breast Cancer Patients. Cancer Invest 2021; 39:597-606. [PMID: 33843402 DOI: 10.1080/07357907.2021.1909059] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Fourty-five breast cancer patients and 50 apparently healthy sex-matched controls from the University of Ilorin Teaching Hospital were enrolled in this study. Plasma D-dimer and fibrinogen were found to be significantly higher than controls; APTT was significantly shorter than the controls. D-dimer and fibrinogen were also significantly positively correlated with ECOG, disease stage, lymph node involvement, and tumor size. On multivariate analysis, D-dimer and fibrinogen were found to be independently related to lymph node involvement. This study shows that plasma D-dimer and fibrinogen levels are elevated in breast cancer patients, and both are markers of disease progression.
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Affiliation(s)
- Ogochukwu O Izuegbuna
- Department of Haematology and Blood Transfusion, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | - Olayide S Agodirin
- Department of Surgery, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | - Hannah O Olawumi
- Department of Haematology and Blood Transfusion, University of Ilorin Teaching Hospital, Ilorin, Nigeria
| | - Samuel A Olatoke
- Department of Surgery, University of Ilorin Teaching Hospital, Ilorin, Nigeria
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21
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Li H, Vanarsa K, Zhang T, Soomro S, Cicalese PA, Duran V, Dasari S, Lee KH, Pedroza C, Kisiel JB, Qin H, Bresalier RS, Chia N, Mohan C. Comprehensive aptamer-based screen of 1317 proteins uncovers improved stool protein markers of colorectal cancer. J Gastroenterol 2021; 56:659-672. [PMID: 34117903 DOI: 10.1007/s00535-021-01795-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/19/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND To screen and validate novel stool protein biomarkers of colorectal cancer (CRC). METHODS A novel aptamer-based screen of 1317 proteins was used to uncover elevated proteins in the stool of patients with CRC, as compared to healthy controls (HCs) in a discovery cohort. Selected biomarker candidates from the discovery cohort were ELISA validated in three independent cross-sectional cohorts comprises 76 CRC patients, 15 adenoma patients, and 63 healthy controls, from two different ethnicities. The expression of the potential stool biomarkers within CRC tissue was evaluated using single-cell RNA-seq datasets. RESULTS A total of 92 proteins were significantly elevated in CRC samples as compared to HCs in the discovery cohort. Among Caucasians, the 5 most discriminatory proteins among the 16 selected proteins, ordered by their ability to distinguish CRC from adenoma and healthy controls, were MMP9, haptoglobin, myeloperoxidase, fibrinogen, and adiponectin. Except myeloperoxidase, the others were significantly associated with depth of tumor invasion. The 8 stool proteins with the highest AUC values were also discriminatory in a second cohort of Indian CRC patients. Several of the stool biomarkers elevated in CRC were also expressed within CRC tissue, based on the single-cell RNA-seq analysis. CONCLUSIONS Stool MMP9, fibrinogen, myeloperoxidase, and haptoglobin emerged as promising CRC stool biomarkers, outperforming stool Hemoglobin. Longitudinal studies are warranted to assess the clinical utility of these novel biomarkers in early diagnosis of CRC.
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Affiliation(s)
- Hao Li
- Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Biomedical Engineering, University of Houston, Houston, USA
| | - Kamala Vanarsa
- Department of Biomedical Engineering, University of Houston, Houston, USA
| | - Ting Zhang
- Department of Biomedical Engineering, University of Houston, Houston, USA
| | - Sanam Soomro
- Department of Biomedical Engineering, University of Houston, Houston, USA
| | | | - Valeria Duran
- Department of Biomedical Engineering, University of Houston, Houston, USA
| | - Shobha Dasari
- Department of Biomedical Engineering, University of Houston, Houston, USA
| | - Kyung Hyun Lee
- Center for Clinical Research and Evidence-Based Medicine, McGovern Medical School, UT Health Science Center At Houston, Houston, USA
| | - Claudia Pedroza
- Center for Clinical Research and Evidence-Based Medicine, McGovern Medical School, UT Health Science Center At Houston, Houston, USA
| | - John B Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, USA
| | - Huanlong Qin
- Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Robert S Bresalier
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - Nicholas Chia
- Department of Surgical Research, Mayo Clinic, Rochester, USA
| | - Chandra Mohan
- Department of Biomedical Engineering, University of Houston, Houston, USA.
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22
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Shimoyama Y, Umegaki O, Kadono N, Minami T. Presepsin and prognostic nutritional index are predictors of septic acute kidney injury, renal replacement therapy initiation in sepsis patients, and prognosis in septic acute kidney injury patients: a pilot study. BMC Nephrol 2021; 22:219. [PMID: 34118899 PMCID: PMC8199821 DOI: 10.1186/s12882-021-02422-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 06/03/2021] [Indexed: 12/30/2022] Open
Abstract
Background Sepsis is the most common cause of acute kidney injury (AKI) among critically ill patients. This study aimed to determine whether presepsin is a predictor of septic acute kidney injury, renal replacement therapy initiation (RRTi) in sepsis patients, and prognosis in septic AKI patients. Methods Presepsin values were measured immediately after ICU admission (baseline) and on Days 2, 3, and 5 after ICU admission. Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, Prognostic Index, and Prognostic Nutritional Index (PNI) were measured at baseline, and total scores (“inflammation-presepsin scores [iPS]”) were calculated for category classification. Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with and without septic AKI or RRTi and between survivors and non-survivors. Results Receiver operating characteristic curve analyses identified the following variables as predictors of septic AKI and RRTi in sepsis patients: presepsin on Day 1 (AUC: 0.73) and Day 2 (AUC: 0.71) for septic AKI, and presepsin on Day 1 (AUC: 0.71), Day 2 (AUC: 0.9), and Day 5 (AUC: 0.96), Δpresepsin (Day 2 – Day 1) (AUC: 0.84), Δpresepsin (Day 5 – Day 1) (AUC: 0.93), and PNI (AUC: 0.72) for RRTi. Multivariate logistic regression analyses identified presepsin on Day 2 as a predictor of prognosis in septic AKI patients. Conclusions Presepsin and PNI were found to be predictors of septic AKI, RRTi in sepsis patients, and prognosis in septic AKI patients.
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Affiliation(s)
- Yuichiro Shimoyama
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
| | - Osamu Umegaki
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan
| | - Noriko Kadono
- Department of Anesthesiology, Osaka Medical College, Intensive Care Unit, Osaka Medical College Hospital, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan
| | - Toshiaki Minami
- Department of Anesthesiology, Osaka Medical College, Osaka Medical College Hospital, Takatsuki, Japan
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23
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Maruyama S, Koda M, Matono T, Isomoto H. Association of tumor size and internal echo pattern with coagulopathy associated with hepatic hemangioma. Mol Clin Oncol 2021; 14:83. [PMID: 33758664 PMCID: PMC7947948 DOI: 10.3892/mco.2021.2245] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 02/05/2021] [Indexed: 01/18/2023] Open
Abstract
Little is known concerning causal factors associated with the size and echogenicity of hepatic hemangiomas. The aim of the present study was to investigate the associations between tumor size and echo pattern and coagulation factors, and to elucidate the growth pattern of hemangiomas. In 214 consecutive patients with hepatic hemangiomas, ultrasonography was performed to determine total tumor number, size, echogenicity and location, and serum laboratory tests for liver function and coagulation factors were carried out. The ultrasonographic appearance of hemangiomas was homogeneous in 75.7% of cases and mixed in 24.3% of cases. A mixed echo pattern was seen in 1 out of 145 masses (0.7%) with a diameter <20 mm, in 30 out of 48 (62.5%) with a diameter of 20-40 mm, and in all of the 21 (100%) with a diameter >40 mm. Platelet counts (P<0.0001) and fibrinogen levels (P<0.01) were lower in patients with larger and mixed tumors. Levels of thrombin-antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDP) were significantly elevated along with an increase in tumor size (all P<0.0001), and the number of patients with the abnormal values of TAT, D-dimer, and FDP was significantly higher in the mixed group than in the homogeneous group (all P<0.0001). Fibrinogen (P<0.01), platelet count (P<0.001), portal vein diameter (P<0.0001), splenic index (P<0.01), and levels of TAT, D-dimer and FDP (all P<0.0001) were significantly associated with tumor size. Multivariate analysis revealed TAT, D-dimer and FDP as independent predictors of tumor size. The internal echo pattern became mixed as size increased. The size and echogenicity of hemangiomas were closely associated with coagulation factors. Therefore, it was speculated that differences in size and echogenicity were caused by intratumoral thrombosis and subsequent hemorrhage.
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Affiliation(s)
- Shigeo Maruyama
- Department of Internal Medicine, Maruyama Medical Clinic, Hamada, Shimane 697-0034, Japan
| | - Masahiko Koda
- Department of Internal Medicine, Hino Hospital, Hino, Tottori 689-4504, Japan
| | - Tomomitsu Matono
- Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan
| | - Hajime Isomoto
- Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan
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Papila Kundaktepe B, Papila C. The clinical significance of preoperative plasma fibrinogen levels and platelet counts in resectable colon cancer. World J Surg Oncol 2021; 19:69. [PMID: 33706789 PMCID: PMC7953657 DOI: 10.1186/s12957-021-02180-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 03/02/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND AND AIM Several aspects of the correlation between colon cancer and hemostatic markers are still unknown to many researchers in the field. In this study, we evaluated the association, if any, of preoperative platelet (PLT) counts and plasma fibrinogen levels with postoperative lymph node involvement and venous invasion in colon cancer patients. METHODS This study retrospectively included eighty patients with colon cancer (mean age 58.09 years; 37% female 63% male). RESULTS Patients with negative lymph nodes and venous invasion showed a significantly lower PLT count and higher fibrinogen level than their counterparts, i.e., patients with positive lymph nodes (p<0.001, all of them) and venous invasion (p<0.001, all of them). The results also showed a positive association of PLT counts and fibrinogen levels with lymphatic invasion (r=0.670, p<0.001 and r=0.639, p<0.001, respectively) and a positive association of PLT counts and fibrinogen levels with venous invasion (r=0.3988, p<0.001 and r=0.5268, p<0.001, respectively). According to the results of the ROC curve analysis, when the PLT count cutoff was 290/mm3, the sensitivity and specificity were 82% and 86.67%, respectively (AUC = 0.8840, p<0.0001, 95% CI 0.8084-0.9596). When the fibrinogen level cutoff was 310.0 mg/dL, the sensitivity and specificity were 72% and 96.67%, respectively (AUC 0.8790, p <0.0001, 95% CI 0.8067-0.9513). CONCLUSION The preoperative PLT count and plasma fibrinogen level may be considered key markers to monitor postoperative lymph node involvement and venous invasion in colon cancer patients.
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Affiliation(s)
- Berrin Papila Kundaktepe
- Department of General Surgery, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey.
| | - Cigdem Papila
- Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
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25
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Ojima Y, Harano M, Sumitani D, Yoshimitsu M, Okajima M. Prognostic value of preoperative carcinoembryonic antigen and D-dimer concentrations in patients undergoing curative resection for colorectal cancer. Surg Today 2021; 51:1108-1117. [PMID: 33386463 DOI: 10.1007/s00595-020-02187-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 11/07/2020] [Indexed: 11/30/2022]
Abstract
PURPOSE Carcinoembryonic antigen (CEA) has limited value as a standalone predictor of the survival in patients with colorectal cancer (CRC). D-dimer (DD) is a predictor of the survival in patients with metastatic CRC. We aimed to predict the prognosis in patients undergoing curative resection for the treatment of CRC by integrating the evaluation of preoperative CEA and DD concentrations with the pathological classification for stage grouping (pStage). METHODS The study enrolled 304 patients between 2007 and 2012. The Combination of DD and CEA Score (CDCS) awarded 1 point each for a CEA concentration of > 5.0 ng/ml and DD concentration of > 1.0 μg/ml. Patients were classified according to the total points: CDCS 2, increased DD and CEA concentrations; CDCS 1, increased concentration of either DD or CEA; CDCS 0, normal concentrations. RESULTS The overall survival (OS) and relapse-free survival (RFS) were significantly lower in patients with CDCS 2 than in those with CDCS 1 or 0. The pStage and CDCS were not independent prognostic predictors of the OS but were predictors of the RFS. The C-index value of the combination of the pStage and CDCS was better than that of either alone for the OS and RFS. CONCLUSION The combination of the pStage and CDCS accurately predicts relapse in patients with CRC.
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Affiliation(s)
- Yasutomo Ojima
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, Hiroshima, Japan.
- Department of Surgery, Yoshijima Hospital, 3-2-33 Yoshijimahigashi, Naka-ku, Hiroshima, Hiroshima, Japan.
| | - Masao Harano
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, Hiroshima, Japan
| | - Daisuke Sumitani
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, Hiroshima, Japan
| | - Masanori Yoshimitsu
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, Hiroshima, Japan
| | - Masazumi Okajima
- Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, Hiroshima, Japan
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Sun Y, Han W, Song Y, Gao P, Yang Y, Yu D, Wang Y, Wang Z. Prognostic Value of Preoperative Fibrinogen for Predicting Clinical Outcome in Patients with Nonmetastatic Colorectal Cancer. Cancer Manag Res 2020; 12:13301-13309. [PMID: 33380836 PMCID: PMC7767646 DOI: 10.2147/cmar.s275498] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 12/03/2020] [Indexed: 01/05/2023] Open
Abstract
Background The prognostic role of preoperative fibrinogen in colorectal cancer (CRC) patients remains controversial. Therefore, we assessed the predictive value of preoperative fibrinogen and developed a tool for predicting the survival of CRC patients. Methods This retrospective study evaluated 1869 patients who underwent curative resection for CRC. Univariate and multivariate survival analyses were conducted to identify the factors correlated with overall survival (OS) and cancer-specific survival (CSS). Nomograms were developed as a graphical representation of the Cox proportional hazards regression models. The performance of the nomograms was assessed by Harrell’s concordance index (c-index) and calibration plots. Results The preoperative fibrinogen levels were correlated with age, tumor differentiation, tumor location, pT category, and TNM stage. In the multivariate analysis, elevated fibrinogen level was independently correlated with worse OS and CSS (OS: hazard ratio [HR] = 0.777, 95% confidence interval [95% CI] = 0.630–0.958, P = 0.018; CSS: HR = 0.757, 95% CI = 0.605–0.947, P = 0.015). The nomograms could predict outcomes with a c-index for OS and CSS of 0.79 and 0.81, respectively. The nomograms also had a good calibration. Conclusion Preoperative fibrinogen level was an independent marker of poor prognosis in patients with nonmetastatic CRC, and there was a threshold level for the use of fibrinogen as a prognostic factor. Furthermore, nomograms may help predict the individual risk of OS and CSS in patients treated for CRC.
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Affiliation(s)
- Yu Sun
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People's Republic of China
| | - Weiying Han
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People's Republic of China
| | - Yongxi Song
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People's Republic of China
| | - Peng Gao
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People's Republic of China
| | - Yuchong Yang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People's Republic of China
| | - Dehao Yu
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People's Republic of China
| | - Yu Wang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People's Republic of China
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, First Hospital of China Medical University, Shenyang City 110001, People's Republic of China
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Li R, Sun Z, Song S, He X, Shi X, Li Z, Song J. NARFIB: A Novel Prognostic Score Based on the Neutrophil-to-Albumin Ratio and Fibrinogen Can Predict the Prognosis of Gastrointestinal Stromal Tumors. Cancer Manag Res 2020; 12:11183-11190. [PMID: 33177869 PMCID: PMC7650032 DOI: 10.2147/cmar.s281375] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 10/08/2020] [Indexed: 12/16/2022] Open
Abstract
Objective The neutrophil-to-albumin ratio (NAR) and fibrinogen are significantly related to tumor progression. The present study evaluated the prognostic impact of the NAR plus fibrinogen concentration in gastrointestinal stromal tumor (GIST) cases. Methods The baseline characteristics, postoperative NAR, and fibrinogen concentrations were retrospectively analyzed for 229 Chinese patients who underwent radical gastrectomy for GIST. Receiver operating characteristic (ROC) curves were applied to estimate the optimal critical points for NAR and fibrinogen. Cox regression analysis was applied to determine significant prognostic variables. Results Multivariate analyses revealed that poor recurrence-free survival was associated with elevated values for fibrinogen (hazard ratio [HR]: 5.015, 95% confidence interval [CI]: 1.993-12.619, P=0.001) and NAR (HR: 4.669, 95% CI: 1.776-12.273, P = 0.002). Combining fibrinogen and the NAR into the NARFIB score provided an area under the ROC curve of 0.833, which was greater than the areas for NAR (0.708) or fibrinogen (0.778). When the NAR and fibrinogen were replaced by the NARFIB score in the multivariate analysis, the independent prognosticators were tumor site (HR: 2.927, 95% CI: 1.417-6.045, P=0.004), mitotic index (HR: 2.661, 95% CI: 1.110-6.380, P=0.028), and the NARFIB score (HR: 14.116, 95% CI: 3.243-61.443, P<0.001). The NARFIB score retained its prognostic significance in various subgroup analyses and was significantly related to gender, surgical approach, tumor size, mitosis, tumor site, risk classification, and recurrence. Conclusion These results suggest that the NARFIB score may help guide prognostication and risk stratification for GIST, which might benefit from targeted therapy.
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Affiliation(s)
- Rui Li
- Department of General Surgery, Beijing Hospital, Peking University Fifth School of Clinical Medicine, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Zhen Sun
- Department of General Surgery, Beijing Hospital, Peking University Fifth School of Clinical Medicine, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Shibo Song
- Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, People's Republic of China
| | - Xiuwen He
- Department of General Surgery, Beijing Hospital, Peking University Fifth School of Clinical Medicine, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Xiaolei Shi
- Department of General Surgery, Beijing Hospital, Peking University Fifth School of Clinical Medicine, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Zhe Li
- Department of General Surgery, Beijing Hospital, Peking University Fifth School of Clinical Medicine, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Jinghai Song
- Department of General Surgery, Beijing Hospital, Peking University Fifth School of Clinical Medicine, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
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Zhang X, Zhao W, Chen X, Zhao M, Qi X, Li G, Shen A, Yang L. Combining the Fibrinogen-to-Pre-Albumin Ratio and Prognostic Nutritional Index (FPR-PNI) Predicts the Survival in Elderly Gastric Cancer Patients After Gastrectomy. Onco Targets Ther 2020; 13:8845-8859. [PMID: 32982279 PMCID: PMC7500527 DOI: 10.2147/ott.s264199] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 07/17/2020] [Indexed: 01/19/2023] Open
Abstract
Background Inflammation and nutrition are important causes contributing to the progression and poor survival of gastric cancer (GC). The objective of this study is to investigate the prognostic significance of the preoperative fibrinogen-to-pre-albumin ratio (FPR) and the prognostic nutritional index (PNI) in GC patients who have undergone gastrectomy. Methods A total of 274 patients with resected pathological GC from January 2007 to December 2013 were enrolled in this retrospective study. Survival analysis was performed using Kaplan–Meier and log rank tests. Univariate and multivariate analyses were established to identify independent prognostic factors of 5-year survival. A predictive nomogram was used to predict prognosis of overall survival (OS), and its accuracy was determined by Harrell’s concordance index (C index). Results A high preoperative FPR-PNI score was significantly correlated with age, bigger tumor size, more lymphatic metastases and advanced TNM stage. Univariate analysis revealed that the GC patients with high FPR, low PNI and high FPR-PNI scores had shorter survival time. Multivariate analysis showed that FPR-PNI was an independent prognostic factor for OS in GC patients, especially in elderly patients. In the sub-analysis by age, the FPR-PNI score could significantly increase the accuracy of prognosis compared with the FPR and PNI alone in elderly GC patients. Conclusion The preoperative FPR-PNI score is an effective independent prognostic index for GC patients after surgery, especially in elderly patients.
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Affiliation(s)
- Xunlei Zhang
- Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong Jiangsu, People's Republic of China
| | - Wenjing Zhao
- Cancer Research Center, Affiliated Tumor Hospital of Nantong University, Nantong Jiangsu, People's Republic of China
| | - Xin Chen
- Department of General Surgery, Affiliated Tumor Hospital of Nantong University, Nantong Jiangsu, People's Republic of China
| | - Min Zhao
- Department of Pathology, Affiliated Tumor Hospital of Nantong University, Nantong Jiangsu, People's Republic of China
| | - Xue Qi
- Department of Oncology, Nantong Liangchun Hospital of Traditional Chinese Medicine, Nantong, Jiangsu, People's Republic of China
| | - Guoxing Li
- Department of General Surgery, Affiliated Tumor Hospital of Nantong University, Nantong Jiangsu, People's Republic of China
| | - Aiguo Shen
- Cancer Research Center, Affiliated Tumor Hospital of Nantong University, Nantong Jiangsu, People's Republic of China
| | - Lei Yang
- Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong Jiangsu, People's Republic of China
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Li M, Bai J, Wang S, Zhai Y, Zhang S, Li C, Du J, Zhang Y. Prognostic Value of Cumulative Score Based on Preoperative Fibrinogen and Albumin Level in Skull Base Chordoma. Onco Targets Ther 2020; 13:8337-8346. [PMID: 32903874 PMCID: PMC7445498 DOI: 10.2147/ott.s257779] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 07/30/2020] [Indexed: 12/18/2022] Open
Abstract
Objective Inflammation and malnutrition have been shown to be correlated with tumor progression and a poor prognosis in various cancers. However, the clinical implications of biomarkers of inflammation and malnutrition in chordoma have not been elucidated. We attempted to characterize the fibrinogen and albumin levels in skull base chordoma and investigate their correlations with clinicopathological data and survival. Methods The preoperative levels of fibrinogen and albumin were assessed in 183 primary skull base chordoma patients. The cutoff values were determined by X-tile software, and their correlations with patient prognosis were further explored using the Kaplan–Meier curve and Cox proportional hazards regression analysis. In addition, the predictive performances of these markers in survival were evaluated by receiver operating characteristic curves. Results The values of fibrinogen and albumin in skull base chordoma patients ranged from 1.73 to 7.40 and 37.6 to 53.0 g/L, respectively. The optimal cutoff values for fibrinogen and albumin were 3.29 and 44.60 g/L, respectively. Fibrinogen and albumin were correlated with the patient age and tumor pathology types. Albumin, but not fibrinogen, was associated with the patients’ progression-free survival and overall survival. Importantly, the FA score, which combines fibrinogen and albumin, could independently predict both progression-free survival and overall survival, and enhanced the performance of fibrinogen or albumin in survival prediction in skull base chordoma. Conclusion Our data reveal the clinical prognostic role of albumin and suggest that the FA score may be a valuable prognostic grading system in skull base chordoma.
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Affiliation(s)
- Mingxuan Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China
| | - Jiwei Bai
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Shuai Wang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China
| | - Yixuan Zhai
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Shuheng Zhang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China
| | - Chuzhong Li
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China
| | - Jiang Du
- Department of Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China
| | - Yazhuo Zhang
- Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China.,Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.,Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, People's Republic of China.,China National Clinical Research Center for Neurological Diseases, Beijing, People's Republic of China.,Key Laboratory of Central Nervous System Injury Research, Capital Medical University, Beijing, People's Republic of China
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Zeng KN, Zhang YC, Wang GS, Zhang J, Deng YN, Li SH, Zhang Q, Li H, Wang GY, Yang Y, Chen GH. A scoring model based on plasma fibrinogen concentration for predicting recurrence of hepatocellular carcinoma after liver transplantation. LIVER RESEARCH 2019; 3:234-239. [DOI: 10.1016/j.livres.2019.11.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Fibrinogen and Albumin Score Changes during Preoperative Treatment Can Predict Prognosis in Patients with Locally Advanced Rectal Cancer. Gastroenterol Res Pract 2019; 2019:3514586. [PMID: 31814824 PMCID: PMC6877962 DOI: 10.1155/2019/3514586] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 10/21/2019] [Indexed: 12/24/2022] Open
Abstract
Background Fibrinogen (Fib) and albumin (Alb) levels are indicators of systemic inflammatory responses. Elevated Fib and decreased Alb levels are considered negative prognostic factors in different types of cancer. Here, we explored the prognostic value of changes in pre- and post- neoadjuvant chemoradiotherapy (NCRT) plasma fibrinogen and serum albumin (FA) scores in patients with locally advanced rectal cancer (LARC). Methods A total of 106 patients with LARC who underwent NCRT followed by surgical resection at Jinhua Municipal Central Hospital between 2011 and 2015 were analyzed. In addition, plasma Fib and serum Alb levels before and after NCRT were collected. FA scores were calculated based on the Fib and Alb levels dichotomized by clinical reference values. Patients were classified into two groups based on the changes in FA scores during NCRT: in group A, FA scores decreased or remained unchanged (n = 84), and in group B, FA scores increased (n = 22). Changes in FA scores were compared with patient outcomes. Results Increased FA scores were associated with worse disease-free survival (DFS) and overall survival (OS) in patients with LARC. The occurrence of systemic failure was higher in group B than in group A (40.9% vs. 19%, P = 0.032). In multivariate analysis, changes in FA scores, pretreatment carcinoembryonic antigen (CEA) levels, and pathologic differentiation were independent prognostic parameters for DFS and changes in FA scores and pretreatment CEA levels were independent prognostic parameters for OS. Conclusions Increased FA score after NCRT was an independent negative prognostic factor for DFS and OS in patients with NCRT-treated LARC.
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Huang C, Liu Z, Xiao L, Xia Y, Huang J, Luo H, Zong Z, Zhu Z. Clinical Significance of Serum CA125, CA19-9, CA72-4, and Fibrinogen-to-Lymphocyte Ratio in Gastric Cancer With Peritoneal Dissemination. Front Oncol 2019; 9:1159. [PMID: 31750248 PMCID: PMC6848261 DOI: 10.3389/fonc.2019.01159] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 10/17/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Relevant serum tumor markers have been indicated to be associated with peritoneal dissemination (PD) of gastric cancer (GC). Fibrinogen has been shown to play an important role in the systemic inflammatory response (SIR) and in tumor progression. However, the clinical significance of the fibrinogen-to-lymphocyte ratio (FLR) in GC with PD has not been studied. Methods: The clinical data of 391 patients with GC were collected, including 86 cases of PD. Then, 1:3 matching was performed by propensity score matching (PSM), and the clinical data of the matched 344 patients were analyzed by univariate and multivariate conditional logistic regression. Classification tree analysis was used to obtain the decision rules and a random forest algorithm to extract the important risk factors of PD in GC. A nomogram model for risk assessment of PD in GC was established by using the rms package of R software. Results: Univariate analysis showed that the factors related to PD in GC were: carbohydrate antigen (CA) 125 (P < 0.0001), CA19-9 (P < 0.0001), CA72-4 (P < 0.0001), FLR (P < 0.0001), neutrophil-to-lymphocyte ratio (NLR) (P < 0.0001), albumin-to- lymphocyte ratio (ALR) (P < 0.0001), platelet-to-lymphocyte ratio (PLR) (P = 0.013), and carcinoembryonic antigen (CEA) (P = 0.031). Conditional logistic regression found that CA125 (OR: 1.046; P < 0.0001), CA19-9 (OR: 1.002; P < 0.0001), and FLR (OR: 1.266; P = 0.024) were independent risk factors for GC with PD. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the decision rules for detecting PD of GC were 89.5, 77.4, 94.0, 82.8, and 91.8%, respectively. According to the important variables identified by the classification tree and random forest algorithm, the risk assessment model of PD in GC was established. The accuracy, sensitivity, and specificity of the model were 91, 89.5, and 79.5%, respectively. Conclusion: CA125 > 17.3 U/ml, CA19-9 > 27.315 U/ml, and FLR > 2.555 were the risk factors for GC with PD. The decision rules and nomogram model constructed by CA125, CA19-9, CA72-4, and FLR can correctly predict the risk of PD in GC.
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Affiliation(s)
| | | | | | | | | | | | | | - Zhengming Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Zhang JB, Wang HH, Wang WB, Wang HY, Lu YM, Yu XF, Teng LS. Association of prealbumin/fibrinogen ratio with clinicopathologic characteristics of gastric cancer. Shijie Huaren Xiaohua Zazhi 2019; 27:1133-1141. [DOI: 10.11569/wcjd.v27.i18.1133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Previous studies have shown that prealbumin (PA) and fibrinogen (Fib) can be used to predict the clinicopathological features and prognosis of a variety of malignant tumors. Therefore, we speculated that the prealbumin-to-fibrinogen ratio (PA/F) can predict the clinicopathological features of patients with gastric cancer (GC) and tumor progression preoperatively.
AIM To explore the relationship between the PA/F ratio and clinicopathological features of patients with GC.
METHODS The preoperative clinical and pathological data of 210 patients with GC admitted to the First Affiliated Hospital of Zhejiang University from January 2017 to March 2019 were retrospectively analyzed. The patients were divided into either a low PA/F group or high PA/F group. The differences in clinical data and pathological features were compared between the two groups, and the correlation between PA/F values and other prognosis-related immunonutrient indicators was also analyzed.
RESULTS The PA/F ratio was significantly associated with age, tumor size, degree of differentiation, depth of invasion, lymph node metastasis, TNM stage, and neurovascular invasion (P < 0.05). The low PA/F value group showed greater age, larger tumor diameter, lower degree of differentiation, deeper infiltration, advanced TNM stage, and more frequent neurovascular invasion (P < 0.05). PA/F values were negatively correlated with multiple immune nutrition indicators, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), and systemic immune-inflammation index (SII), but positively correlated with prognostic nutritional index (PNI).
CONCLUSION The PA/F ratio can be used as a predictor of preclinical clinicopathological features in patients with GC, and patients with a PA/F ratio ≤ 9.07 have a relatively poor prognosis. The PA/F value is associated with NLR, PLR, CAR, SII, and PNI.
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Affiliation(s)
- Jun-Bin Zhang
- Department of Surgical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Hao-Hao Wang
- Department of Surgical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Wei-Bin Wang
- Department of Surgical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Hai-Yong Wang
- Department of Surgical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Yi-Min Lu
- Department of Surgical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Xiong-Fei Yu
- Department of Surgical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Li-Song Teng
- Department of Surgical Oncology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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Drizlionoka K, Zariņš J, Ozoliņa A, Ņikitina-Zaķe L, Mamaja B. Polymorphism rs2066865 in the Fibrinogen Gamma Chain ( FGG) Gene Increases Plasma Fibrinogen Concentration and Is Associated with an Increased Microvascular Thrombosis Rate. ACTA ACUST UNITED AC 2019; 55:medicina55090563. [PMID: 31484330 PMCID: PMC6780972 DOI: 10.3390/medicina55090563] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 08/21/2019] [Accepted: 08/30/2019] [Indexed: 11/17/2022]
Abstract
Background and Objective: Thrombosis due to inherited hypercoagulability is an issue that has been raised in microvascular flap surgery previously. We analyzed the association of a single nucleotide polymorphism (SNP) in rs2066865 in the fibrinogen gamma chain (FGG) gene, alteration in plasma fibrinogen concentration, and presence of microvascular flap thrombosis. Materials and Methods: A total of 104 adult patients with microvascular flap surgery were subjected to an analysis of the presence of SNP rs2066865 in the FGG gene. Alterations in plasma fibrinogen concentration according to genotype were determined as a primary outcome, and flap thrombosis was defined as a secondary outcome. Results: Flap thrombosis was detected in 11.5% of patients (n = 12). Successful revision of anastomosis was performed in four patients, resulting in a microvascular flap survival rate of 92.3%. We observed an increase in plasma fibrinogen concentration in genotype G/A and A/A carriers (G/G, 3.9 (IQR 4.76-3.04); G/A, 4.28 (IQR 5.38-3.18); A/A, 6.87 (IQR 8.25-5.49) (A/A vs. G/A, p = 0.003 and A/A vs. G/G, p = 0.001). Within group differences in microvascular flap thrombosis incidence rates were observed—G/G 6/79 (7.59%); G/A 5/22 (22.7%); A/A 1/3 (33.3%) (OR 0.30 95%; CI 0.044 to 0.57), p = 0.016; RR 3.2—when G/G versus G/A and A/A were analyzed respectively. Conclusions: A/A and G/A genotype carriers of a single nucleotide polymorphism in rs2066865 in the fibrinogen gamma chain gene had a higher plasma fibrinogen concentration, and this might be associated with an increased microvascular flap thrombosis incidence rate. Determined polymorphism could be considered as a genetic marker associated with microvascular flap thrombosis development. To confirm the results of this study, the data should be replicated in a greater sample size.
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Affiliation(s)
- Karina Drizlionoka
- Department of Anaesthesiology, Riga East Clinical University Hospital, LV-1024 Riga, Latvia.
| | - Jānis Zariņš
- Centre of Plastic and Reconstructive Microsurgery of Latvia, LV-1024 Riga, Latvia
| | - Agnese Ozoliņa
- Department of Anaesthesiology and Critical Care, Riga Stradins University, LV-1007 Riga, Latvia
| | | | - Biruta Mamaja
- Department of Anaesthesiology, Riga East Clinical University Hospital, LV-1024 Riga, Latvia
- Department of Anaesthesiology and Critical Care, Riga Stradins University, LV-1007 Riga, Latvia
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Li M, Wu Y, Zhang J, Huang L, Wu X, Yuan Y. Prognostic value of pretreatment plasma fibrinogen in patients with colorectal cancer: A systematic review and meta-analysis. Medicine (Baltimore) 2019; 98:e16974. [PMID: 31517816 PMCID: PMC6750243 DOI: 10.1097/md.0000000000016974] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 07/13/2019] [Accepted: 08/05/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Growing evidence showed that high pretreatment plasma fibrinogen could be used as a potential prognostic marker in colorectal cancer (CRC). However, the conclusions were controversial. Therefore, this meta-analysis was conducted to evaluate the prognostic value of pretreatment plasma fibrinogen in patients with CRC. METHODS Relevant studies were searched in the databases including PubMed, EMBASE, Web of Science, Cochrane library, and China National Knowledge Infrastructure up until December 10th, 2018. Pooled hazard ratios (HRs) with their 95% confidence intervals (CIs) were used to estimate the effects. RESULTS A total of 17 articles with 6863 patients were included in this meta-analysis. The results revealed that elevated pretreatment plasma fibrinogen was significantly associated with both poor overall survival (univariate analysis: HR = 1.69, 95% CI 1.47-1.95, P = .000; multivariate analysis: HR = 1.50, 95% CI 1.28-1.77, P = .000) and poor disease-free survival (univariate analysis: HR = 1.90, 95% CI 1.49-2.41, P = .000; multivariate analysis: HR = 2.08, 95% CI 1.52-2.86, P = .000) in patients with CRC. CONCLUSIONS High pretreatment plasma fibrinogen level is significantly associated with worse survival outcomes in CRC patients. Plasma fibrinogen may be used as an effective prognostic marker and potential therapeutic target. Further studies are required to support these results.
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Affiliation(s)
- Menglei Li
- The Department of Clinical Laboratory Medicine, Yongchuan Hospital, Chongqing Medical University
| | - Yang Wu
- The Department of Clinical Laboratory Medicine, Yongchuan Hospital, Chongqing Medical University
| | - Jiwang Zhang
- The Department of Clinical Laboratory Medicine, Yongchuan Hospital, Chongqing Medical University
| | - Lijun Huang
- The Department of Clinical Laboratory Medicine, Yongchuan Hospital, Chongqing Medical University
| | - Xianlan Wu
- The Department of Clinical Laboratory Medicine, southwest Hospital, Third Military Medical University (Army Medical University), ChongQing, China
| | - Yongqiang Yuan
- The Department of Clinical Laboratory Medicine, Yongchuan Hospital, Chongqing Medical University
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Chen Y, Zhu Y, Sheng Y, Xiao J, Xiao Y, Cheng N, Chai Y, Wu X, Zhang S, Xiang T. SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3. Exp Cell Res 2019; 382:111466. [PMID: 31201813 DOI: 10.1016/j.yexcr.2019.06.011] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 06/10/2019] [Accepted: 06/11/2019] [Indexed: 12/21/2022]
Abstract
Renal cell carcinoma (RCC) is one of the common lethal urologic tumors. Recent studies revealed that SIRT1 might function as a tumor suppressor during the progression of RCC. In addition, studies showed that FGB expression was abnormally upregulated in RCC and related to the progress of RCC. This study aimed to define the function of SIRT1 and underlying mechanism in the RCC progression. The expression of SIRT1 and FGB in RCC specimens and cells were detected by immunoblotting and immunostaining. Luciferase reporter assay was performed to confirm FGB as the target gene of STAT3. Other methods including stable transfection, co-immunoprecipitation, Western blot, and in vitro and in vivo proliferation assays were also performed. Our results showed that SIRT1 expression was downregulated in RCC tissues compared to adjacent normal tissues and relatively high expression of SIRT1 conferred a better prognosis for patients. Next, we showed that SIRT1 overexpression inhibited RCC tumorigenesis both in vitro and in vivo. In addition, FGB expression was upregulated in RCC tissues and overexpressing SIRT1 reduced FGB expression levels. Furthermore, inhibition of RCC proliferation by SIRT1 overexpression was rescued by FGB overexpression, indicating that SIRT1 inhibited RCC proliferation by repressing FGB expression. Mechanistically, we confirmed that FGB was the target gene of STAT3, and SIRT1 repressed the expression of FGB by deacetylation of STAT3, leading to STAT3 destabilization and degradation. SIRT1 inhibited RCC tumorigenesis by downregulating FGB expression, and this novel SIRT1-STAT3-FGB axis provided a potential target for RCC therapy.
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Affiliation(s)
- Yanbing Chen
- Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Ying Zhu
- Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Yanling Sheng
- Department of Ultrasound, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330006, Jiangxi Province, China
| | - Juhua Xiao
- Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi Province, Jiangxi, 330006, China
| | - Yu Xiao
- Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi Province, Jiangxi, 330006, China
| | - Na Cheng
- Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Yong Chai
- Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi Province, Jiangxi, 330006, China
| | - Xiaoping Wu
- Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Shouhua Zhang
- Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi Province, Jiangxi, 330006, China.
| | - Tianxin Xiang
- Department of Infectious Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
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Clinicopathological and prognostic significance of preoperative plasma fibrinogen level in patients with upper urinary tract urothelial carcinoma: A retrospective tumor marker prognostic study. Int J Surg 2019; 65:88-93. [PMID: 30951871 DOI: 10.1016/j.ijsu.2019.03.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 01/24/2019] [Accepted: 03/24/2019] [Indexed: 11/24/2022]
Abstract
PURPOSE To retrospectively evaluate the prognostic value of preoperative plasma fibrinogen to predict oncological outcome and intravesical recurrence in upper urinary tract urothelial carcinoma. METHODS This retrospective study comprised 130 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent surgery between June 2009 and June 2017 at a single center. Patients were categorized base on an optimal value of preoperative plasma fibrinogen. Progression-free and cancer-specific survival were assessed using Kaplan-Meier method. The associations between plasma fibrinogen and clinical outcomes were assessed with univariate and Multivariate analysis. RESULTS Elevated plasma fibrinogen was associated with advance tumor stage, high tumor grade and tumor size. No significant association was found between plasma fibrinogen and intravesical recurrence. Multivariate analysis revealed that plasma fibrinogen ≥3.602 g/L was an independent prognostic indicator for progression-free survival (HR = 2.18; 95% CI: 1.17-4.06; p = 0.01) and cancer-specific survival (HR = 2.2; 95% CI: 1.13-4.28; p = 0.02), as well as pathological T stage and tumor grade. CONCLUSIONS Elevated preoperative plasma fibrinogen is an independent unfavorable prognostic factor for oncological outcomes in patients with upper urinary tract urothelial carcinoma. However, there is no association between preoperative plasma fibrinogen and intravesical recurrence. As an effective and easily accessible biomarker, this parameter can be applied in pre-intervention risk stratification of upper urinary tract urothelial carcinoma.
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Falanga A, Marchetti M. Hemostatic biomarkers in cancer progression. Thromb Res 2018; 164 Suppl 1:S54-S61. [PMID: 29703485 DOI: 10.1016/j.thromres.2018.01.017] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 01/08/2018] [Accepted: 01/10/2018] [Indexed: 02/06/2023]
Abstract
Malignant disease is characterized by a hemostatic imbalance, usually shifted towards a procoagulant direction, and a high incidence of thrombotic complications. The mechanisms of hemostasis that are critically involved in thrombosis are also implicated in tumor progression, angiogenesis, and metastatic spread. As there is a close relationship between cancer and the clotting system, circulating biomarkers of activation of various hemostasis compartments (i.e. coagulation, fibrinolysis, platelets, endothelium, and other blood cells) have been extensively studied to predict cancer outcomes along with predicting the thrombotic risk. In this review, we will summarize the results of published studies and will focus on ongoing research and future directions of clotting activation bioproducts as biomarkers of cancer disease and progression.
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Affiliation(s)
- Anna Falanga
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.
| | - Marina Marchetti
- Division of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
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Duan S, Gong B, Wang P, Huang H, Luo L, Liu F. Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG. Mol Med Rep 2018; 18:3727-3736. [PMID: 30106150 PMCID: PMC6131538 DOI: 10.3892/mmr.2018.9368] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 08/02/2018] [Indexed: 12/19/2022] Open
Abstract
Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-associated mortality in the world. However, its mechanisms of occurrence and development have not been clearly elucidated. Furthermore, there is no effective tumor marker for GC. Using DNA microarray analysis, the present study revealed genetic alterations, screened out core genes as novel markers and discovered pathways for potential therapeutic targets. Differentially expressed genes (DEGs) between GC and adjacent normal tissues were identified, followed by pathway enrichment analysis of DEGs. Next, the protein-protein interaction (PPI) network of DEGs was built and visualized. Analyses of modules in the PPI network were then performed to identify the functional core genes. Finally, survival analysis of core genes was conducted. A total of 256 genes were identified as DEGs between the GC samples and normal samples, including 169 downregulated and 87 upregulated genes. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the present study identified a total of 143 GO terms and 21 pathways. Six clusters of functional modules were identified, and the genes associated with these modules were screened out as the functional core genes. Certain core genes, including collagen type 12 α1 chain (COL12A1), glutathione S-transferase α3 (GSTA3), fibrinogen α chain (FGA) and fibrinogen γ chain (FGG), were the first reported to be associated with GC. Survival analysis suggested that these four genes, COL12A1 (P=0.002), GSTA3 (P=3.4×10−6), FGA (P=0.00075) and FGG (P=1.4×10-5), were significant poor prognostic factors and therefore, potential targets to improve diagnosis, optimize chemotherapy and predict prognostic outcomes.
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Affiliation(s)
- Shijie Duan
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Baocheng Gong
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Pengliang Wang
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Hanwei Huang
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Lei Luo
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Funan Liu
- Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
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Nasr R, Salim Hammoud M, Nassar F, Mukherji D, Shamseddine A, Temraz S. Inflammatory Markers and MicroRNAs: The Backstage Actors Influencing Prognosis in Colorectal Cancer Patients. Int J Mol Sci 2018; 19:E1867. [PMID: 29949857 PMCID: PMC6073730 DOI: 10.3390/ijms19071867] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 06/17/2018] [Accepted: 06/25/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) remains a deadly disease, afflicting the lives of millions worldwide. The prognosis of CRC patients is best predicted by surgical resection and pathological analysis of specimens. Emerging evidence has attributed a significant role to inflammatory markers and microRNAs (miRNAs) in the prognosis and survival of CRC patients. AIM Here, we review the literature on inflammatory markers and miRNAs with an established role on survival rates, response to systemic chemotherapy, and other clinic-pathological parameters in CRC patients. RESULTS Our literature review revealed a critical role of inflammatory markers—specifically, the acute-phase proteins, inflammatory cytokines, and blood cell ratios—on prognostic outcomes in CRC patients. MiRNAs, on the other hand, were useful in predicting prognosis and clinical response and accordingly stratifying CRC patients for optimal drug selection. CONCLUSION These biomarkers are easily measured in routine blood exams and can be used in adjunct to the tumor-node-metastasis (TNM) staging system to identify high-risk patients and those who are more likely to benefit from chemotherapy and other targeted therapies. However, more prospective studies are needed for the validation of these discussed prognostic and predictive biomarkers.
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Affiliation(s)
- Rihab Nasr
- Department of Internal Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut 110 72020, Lebanon.
| | - Miza Salim Hammoud
- Department of Internal Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut 110 72020, Lebanon.
| | - Farah Nassar
- Department of Internal Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut 110 72020, Lebanon.
| | - Deborah Mukherji
- Department of Internal Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut 110 72020, Lebanon.
| | - Ali Shamseddine
- Department of Internal Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut 110 72020, Lebanon.
| | - Sally Temraz
- Department of Internal Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut 110 72020, Lebanon.
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Ji R, Ren Q, Bai S, Wang Y, Zhou Y. Prognostic significance of pretreatment plasma fibrinogen level in patients with digestive system tumors: a meta-analysis. Int J Biol Markers 2018; 33:254-265. [PMID: 29874984 DOI: 10.1177/1724600818773627] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
High pretreatment levels of plasma fibrinogen have been widely reported to be a potential predictor of prognosis in digestive system tumors; however, the conclusions are not consistent. Therefore, we performed a meta-analysis to comprehensively assess the prognostic roles of high pretreatment plasma fibrinogen levels in digestive system tumors. We searched for eligible studies in the PubMed, Embase, and Web of Science electronic databases for publications from the database inception to 1 September 2017. The endpoints of interest included overall survival, disease-free survival, and recurrence-free survival. We investigated the relationship between fibrinogenemia and overall survival in colorectal cancer (10 studies), gastric cancer (6), pancreatic cancer (6), hepatocellular carcinoma (7), and esophageal squamous cell carcinoma (10); the pooled results indicated that fibrinogenemia was significantly related to a worse overall survival (hazard ratio (HR) 1.73; 95% confidence interval (CI) 1.52, 1.97; P <0.001; HR 1.71; 95% CI 1.28, 2.28; P <0.001; HR 1.57; 95% CI 1.13, 2.17; P = 0.007; HR 1.89; 95% CI 1.57, 2.27; P <0.001, and HR 1.67; 95% CI 1.35, 2.07; P <0.001). Taken together, an increased pretreatment plasma fibrinogen level was related to worse survival in digestive system tumors, indicating that it could be a useful prognostic marker in these types of tumors.
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Affiliation(s)
- Rui Ji
- 1 Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,2 Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Qian Ren
- 1 Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,2 Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Suyang Bai
- 1 Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,2 Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yuping Wang
- 1 Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,2 Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- 1 Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.,2 Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
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43
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Jianyong L, Zhihui L, Rixiang G, Jingqiang Z. Using a nomogram based on preoperative serum fibrinogen levels to predict recurrence of papillary thyroid carcinoma. BMC Cancer 2018; 18:390. [PMID: 29621982 PMCID: PMC5887254 DOI: 10.1186/s12885-018-4296-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 03/22/2018] [Indexed: 02/08/2023] Open
Abstract
Background Hyperfibrinogenemia is increasingly being recognized as an important risk factor related to cancer stage, development and outcomes. We evaluated whether preoperative serum fibrinogen levels predict recurrence of papillary thyroid carcinoma (PTC). Methods We retrospectively collected data for 1023 PTC patients who underwent surgery at our institution from Aug 2014 to Aug 2016. In total, 414 patients (from Aug 2014 to Dec 2015) were used as the training set to build the model, and 609 patients (from Jan 2016 to Aug 2016) were used as the testing set to validate the model. Results In the training set, PTC cases with high serum fibrinogen levels were more likely to have multiple PTCs (P = 0.001) and to exhibit surrounding tissue or organ invasion (both P < 0.01). Moreover, PTC patients with higher serum fibrinogen levels were also more likely to have an advanced tumor stage (T, P = 0.001) and distance metastasis (P < 0.001), and these patients had a significantly higher rate of postoperative PTC recurrence (P = 0.002). All of these findings were validated in the testing set. The results of univariate and multivariate analyses indicated that hyperfibrinogenemia was a risk factor for PTC recurrence. The identified risk factors were incorporated into a nomogram and validated using the testing set (C-index = 0.811, 95% CI: 0.762–0.871). Conclusion PTC cases with hyperfibrinogenemia are more likely to have an advanced TNM stage and have a higher rate of PTC recurrence. Our nomogram could be used to objectively and accurately predict PTC recurrence in a clinical setting.
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Affiliation(s)
- Lei Jianyong
- Thyroid and Parathyroid Surgery Group of West China Hospital of Sichuan University, Chengdu, China
| | - Li Zhihui
- Thyroid and Parathyroid Surgery Group of West China Hospital of Sichuan University, Chengdu, China
| | - Gong Rixiang
- Thyroid and Parathyroid Surgery Group of West China Hospital of Sichuan University, Chengdu, China
| | - Zhu Jingqiang
- Thyroid and Parathyroid Surgery Group of West China Hospital of Sichuan University, Chengdu, China.
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Kaplani K, Koutsi S, Armenis V, Skondra FG, Karantzelis N, Champeris Tsaniras S, Taraviras S. Wound healing related agents: Ongoing research and perspectives. Adv Drug Deliv Rev 2018; 129:242-253. [PMID: 29501699 DOI: 10.1016/j.addr.2018.02.007] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Revised: 01/28/2018] [Accepted: 02/26/2018] [Indexed: 02/07/2023]
Abstract
Wound healing response plays a central part in chronic inflammation, affecting millions of people worldwide. It is a dynamic process that can lead to fibrosis, if tissue damage is irreversible and wound resolution is not attained. It is clear that there is a tight interconnection among wound healing, fibrosis and a variety of chronic disease conditions, demonstrating the heterogeneity of this pathology. Based on our further understanding of the cellular and molecular mechanisms underpinning tissue repair, new therapeutic approaches have recently been developed that target different aspects of the wound healing process and fibrosis. Nevertheless, several issues still need to be taken into consideration when designing modern wound healing drug delivery formulations. In this review, we highlight novel pharmacological agents that hold promise for targeting wound repair and fibrosis. We also focus on drug-delivery systems that may enhance current and future therapies.
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Affiliation(s)
- Konstantina Kaplani
- Division of Stem Cells and Regenerative Medicine, Biomedical Postgraduate Programme, School of Medicine, University of Patras, Patras 26504, Greece; Department of Physiology, School of Medicine, University of Patras, Patras 26504, Greece
| | - Stamatina Koutsi
- Division of Stem Cells and Regenerative Medicine, Biomedical Postgraduate Programme, School of Medicine, University of Patras, Patras 26504, Greece; Department of Physiology, School of Medicine, University of Patras, Patras 26504, Greece
| | - Vasileios Armenis
- Division of Stem Cells and Regenerative Medicine, Biomedical Postgraduate Programme, School of Medicine, University of Patras, Patras 26504, Greece
| | - Foteini G Skondra
- Division of Stem Cells and Regenerative Medicine, Biomedical Postgraduate Programme, School of Medicine, University of Patras, Patras 26504, Greece
| | - Nickolas Karantzelis
- Department of Physiology, School of Medicine, University of Patras, Patras 26504, Greece
| | | | - Stavros Taraviras
- Division of Stem Cells and Regenerative Medicine, Biomedical Postgraduate Programme, School of Medicine, University of Patras, Patras 26504, Greece; Department of Physiology, School of Medicine, University of Patras, Patras 26504, Greece.
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Hong T, Shen D, Chen X, Wu X, Hua D. Preoperative plasma fibrinogen, but not D-dimer might represent a prognostic factor in non-metastatic colorectal cancer: A prospective cohort study. Cancer Biomark 2018; 19:103-111. [PMID: 28269756 DOI: 10.3233/cbm-160510] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUNDS Cancer progression has been associated with host hemostasis system. Whether preoperative plasma hemostasis factors can predict survival in colorectal cancer is quite intriguing. METHODS We conducted a prospective cohort study to validate the prognostic significance of three hemostasis parameters - fibrinogen, fibrin degradation products (FDPs) and D-dimer - in non-metastatic colorectal cancer patients treated with curative resection. RESULTS All three parameters were positively correlated with C reactive protein (CRP) levels and Glasgow Prognostic scores (GPS). In univariate cox hazards regression model, as continuous variables, both fibrinogen (HR: 1.07, 95%CI: 1.01-1.13) and FDPs (HR: 1.17, 95%CI: 1.05-1.31) were prognostic, while D-dimer levels were not. Patients with hyperfibrinogenemia had a 2.12-fold increased mortality risk compared with patients without hyperfibrinogenemia. Patients with positive FDPs had a 3.68-fold increased mortality risk compared with patients with negative FDPs. In multivariate models, hyperfibrinogenemia was prognostic (HR: 3.39, 95%CI: 1.34-8.67) in patients with normal GPS scores. CONCLUSIONS Preoperative fibrinogen levels appeared as an independent mortality risk factor in non-metastatic colorectal cancer patients with normal GPS scores. Fibrinogen could be a reliable marker to identify high risk patients for those without systematic inflammation responses.
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Xie Y, Chen L, Lv X, Hou G, Wang Y, Jiang C, Zhu H, Xu N, Wu L, Lou X, Liu S. The levels of serine proteases in colon tissue interstitial fluid and serum serve as an indicator of colorectal cancer progression. Oncotarget 2018; 7:32592-606. [PMID: 27081040 PMCID: PMC5078036 DOI: 10.18632/oncotarget.8693] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 03/28/2016] [Indexed: 02/06/2023] Open
Abstract
The proteins in tissue interstitial fluids (TIFs) can spread into the blood and have been proposed as an ideal material to find blood biomarkers. The colon TIFs were collected from 8-, 13-, 18-, and 22-week ApcMin/+, a typical mouse model of colorectal cancer (CRC), and wild-type mice. iTRAQ-based quantification proteomics was conducted to survey the TIF proteins whose abundance appeared to depend on tumor progression. A total of 46 proteins that exhibited consecutive changes in abundance were identified, including six serine proteases, chymotrypsin-like elastase 1 (CELA1), chymotrypsin-like elastase 2A (CEL2A), chymopasin, chymotrypsinogen B (CTRB1), trypsin 2 (TRY2), and trypsin 4 (TRY4). The observed increases in the abundance of serine proteases were supported in another quantitative evaluation of the individual colon TIFs using a multiple reaction monitor (MRM) assay. Importantly, the increases in the abundance of serine proteases were also verified in the corresponding sera. The quantitative verification of the serine proteases was further extended to the clinical sera, revealing significantly higher levels of CELA1, CEL2A, CTRL/chymopasin, and TRY2 in CRC patients. The receiver operating characteristic analysis illustrated that the combination of CELA1 and CTRL reached the best diagnostic performance, with 90.0% sensitivity and 80.0% specificity. Thus, the quantitative target analysis demonstrated that some serine proteases are indicative of CRC progression.
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Affiliation(s)
- Yingying Xie
- CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Lechuang Chen
- Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiaolei Lv
- Beijing Protein Innovation, Beijing, 101318, China
| | - Guixue Hou
- CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yang Wang
- CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Cuicui Jiang
- Beijing Protein Innovation, Beijing, 101318, China
| | - Hongxia Zhu
- Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Ningzhi Xu
- Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Lin Wu
- CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xiaomin Lou
- CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Siqi Liu
- CAS Key Laboratory of Genome Sciences and Information, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.,University of Chinese Academy of Sciences, Beijing, 100049, China.,Beijing Protein Innovation, Beijing, 101318, China.,Proteomics Division, BGI-Shenzhen, Shenzhen, Guangdong, 518083, China
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Xu Q, Yan Y, Gu S, Mao K, Zhang J, Huang P, Zhou Z, Chen Z, Zheng S, Liang J, Lin Z, Wang J, Yan J, Xiao Z. A Novel Inflammation-Based Prognostic Score: The Fibrinogen/Albumin Ratio Predicts Prognoses of Patients after Curative Resection for Hepatocellular Carcinoma. J Immunol Res 2018; 2018:4925498. [PMID: 30027102 PMCID: PMC6031154 DOI: 10.1155/2018/4925498] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 01/18/2018] [Accepted: 02/04/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammation is an important hallmark of cancer. Fibrinogen and albumin are both vital factors in systemic inflammation. This study investigated the prognostic value of the fibrinogen/albumin ratio in HCC patients who underwent curative resection. METHODS HCC patients (n = 151) who underwent curative resection were evaluated retrospectively. The optimal cutoff value for the fibrinogen/albumin ratio was selected by receiver operating characteristic (ROC) curve analysis. Correlations between preoperative fibrinogen/albumin ratios and clinicopathologic characteristics were analyzed by χ2 test. The area under the receiver operating characteristic curve (AUC) was calculated to compare the prognostic value of the fibrinogen/albumin ratio with other prognostic scores (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and albumin-bilirubin (ALBI) score). The overall survival (OS) and time to recurrence (TTR) were assessed by the log-rank test and the Cox proportional hazard regression model. RESULTS An optimal cutoff value of the preoperative fibrinogen/albumin ratio (0.062) was determined for 151 patients who underwent curative resection for HCC via a ROC curve analysis. Fibrinogen/albumin ratio > 0.062 was significantly associated with microvascular invasion, an advanced BCLC stage, and ALBI grade. Multivariate analyses revealed that fibrinogen/albumin ratio was an independent predictor for OS (P = 0.003) and TTR (P = 0.035). The prognostic ability of fibrinogen/albumin ratio was comparable to other prognostic scores (NLR, PLR, and ALBI score) by AUC analysis. Patients with a fibrinogen/albumin ratio > 0.062 had lower 1-, 3-, and 5-year OS rates (66.0%, 41.8%, and 28.2% versus 81.9%, 69.3%, and 56.1%, resp., P < 0.001) and higher 1-, 3-, and 5-year recurrence rates (60.9%, 79.2%, and 90.5% versus 49.5%, 69.1%, and 77.1%, resp., P = 0.008) compared with patients with fibrinogen/albumin ratio ≤ 0.062. CONCLUSION The preoperative fibrinogen/albumin ratio is an effective prognostic factor for HCC patients who underwent curative resection. An elevated fibrinogen/albumin ratio significantly correlates with poorer survival and a higher risk of recurrence in HCC patients.
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Affiliation(s)
- Qiaodong Xu
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
- Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou 515041, China
| | - Yongcong Yan
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
| | - Songgang Gu
- Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou 515041, China
| | - Kai Mao
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
| | - Jianlong Zhang
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
| | - Pinbo Huang
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
| | - Zhenyu Zhou
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
| | - Zheng Chen
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
| | - Shaodong Zheng
- Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou 515041, China
| | - Jiahong Liang
- Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou 515041, China
| | - Zhihua Lin
- Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou 515041, China
| | - Jie Wang
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
| | - Jiang Yan
- Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou 515041, China
| | - Zhiyu Xiao
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, No. 107 Yanjiang Western Road, Guangzhou 510120, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289, China
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Liu X, Liu Z, Lin E, Chen Y, Sun X, Zhou Z. A cumulative score based on preoperative fibrinogen and the neutrophil-lymphocyte ratio to predict outcomes in resectable gastric cancer. Cancer Manag Res 2018; 10:3007-3014. [PMID: 30214295 PMCID: PMC6118276 DOI: 10.2147/cmar.s174656] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Recent studies have revealed that preoperative fibrinogen and the neutrophil-lymphocyte ratio (NLR) are associated with poor outcome in gastric cancer (GC). We aimed to evaluate whether the fibrinogen and the NLR score had a consistent prognostic value for resectable GC. METHODS We analyzed 1,293 consecutive patients who underwent curative surgery for GC. The F-NLR score was 2 for patients with hyperfibrinogenemia (>400 mg/dL) and elevated NLR (≥5.0), 1 for those with one abnormal index, and 0 for those with no abnormal indices. RESULTS We found that higher F-NLR scores were associated with larger tumor size, deeper tumor invasion and more lymph node metastasis (all P<0.05). In a multivariate analysis, F-NLR independently predicted postoperative survival (P<0.001). When stratified by tumor-node-metastasis (TNM) stage, the prognostic value of F-NLR was still maintained for stages I-II (P<0.001) and stage III (P=0.003). Of note, F-NLR also effectively stratified overall survival (OS) irrespective of age, adjuvant chemotherapy administration, tumor location and histological grade (all P<0.05). Furthermore, F-NLR and TNM stratified 5-year OS from 61% (F-NLR 0) to 15% (F-NLR 2) and from 92% (stage I) to 37% (stage III), respectively. Utilizing both F-NLR and TNM, 5-year OS ranged from 93% (F-NLR 0, TNM I) to 6% (F-NLR 2, TNM III). CONCLUSION The F-NLR score independently predicts outcomes in GC patients after curative surgery. Therefore, it should be implemented in routine clinical practice for identifying more high-risk patients.
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Affiliation(s)
- Xuechao Liu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China, ;
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China, ;
| | - Zhimin Liu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China, ;
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China, ;
| | - Enzi Lin
- Surgical Oncology Session No. 1, Cancer Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China
| | - Yingbo Chen
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China, ;
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China, ;
| | - Xiaowei Sun
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China, ;
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China, ;
| | - Zhiwei Zhou
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China, ;
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China, ;
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Zhang F, Wang Y, Sun P, Wang ZQ, Wang DS, Zhang DS, Wang FH, Fu JH, Xu RH, Li YH. Fibrinogen promotes malignant biological tumor behavior involving epithelial-mesenchymal transition via the p-AKT/p-mTOR pathway in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 2017; 143:2413-2424. [PMID: 28801734 DOI: 10.1007/s00432-017-2493-4] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2017] [Accepted: 08/04/2017] [Indexed: 12/14/2022]
Abstract
PURPOSE Hyperfibrinogenemia is associated with unfavorable prognosis and advanced tumor behavior in various malignancies, including esophageal squamous cell carcinoma (ESCC). However, its biological function in ESCC is unknown. The present study was designed to further validate the prognostic value of preoperative plasma hyperfibrinogenemia and evaluate the biological role of fibrinogen, as well as the underlying mechanism in ESCC. METHODS Data from 452 cases with newly diagnosed ESCC followed by curative surgery between 2006 and 2010 were retrospectively evaluated. The Clauss method was utilized to measure the preoperative plasma fibrinogen level. Correlations between the fibrinogen level and clinicopathologic characteristics and survival analysis were performed. The effects of fibrinogen on malignant behaviors, including tumor cell viability, colony formation, migration, and invasion, were also investigated. RESULTS The optimal cut-off value for plasma fibrinogen level was defined as 4.0 g/L according to recommendations. Thus, the proportion of hyperfibrinogenemia was 24.8% (112/452). Preoperative plasma hyperfibrinogenemia was significantly associated with advanced tumor length, deep tumor invasion, advanced tumor-node-metastasis stage, alcohol consumption, a higher white blood cell count, a higher platelet count, and high globulin levels. Univariate survival analysis revealed that compared to those with normal plasma fibrinogen levels, patients with hyperfibrinogenemia tended to have poorer disease-free survival (DFS) [hazard ratio (HR), 1.692; 95% confidence interval (CI), 1.304-2.196; P < 0.001] and overall survival (OS) (HR 1.864; 95% CI 1.424-2.440; P < 0.001). In the multivariate Cox regression models, these factors remained independent predictors for impaired DFS (HR 1.491; 95% CI 1.138-1.955; P = 0.004) and OS (HR 1.648; 95% CI 1.246-2.180; P < 0.001) after adjusting for other confounding variables. In addition, fibrinogen could significantly promote cell migration and invasion but not proliferation. Moreover, it could also induce epithelial-mesenchymal transition (EMT) and increase the levels of p-PTEN, p-AKT, and p-mTOR in ESCC cell lines. CONCLUSIONS Preoperative plasma hyperfibrinogenemia might serve as an independent predictor of unfavorable survival in ESCC. Furthermore, fibrinogen may promote cell motility by inducing EMT via the p-AKT/p-mTOR pathway.
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Affiliation(s)
- Fei Zhang
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Yun Wang
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Peng Sun
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Zhi-Qiang Wang
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - De-Shen Wang
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Dong-Sheng Zhang
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Feng-Hua Wang
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Jian-Hua Fu
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Guangdong Esophageal Cancer Institute, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Rui-Hua Xu
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Yu-Hong Li
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People's Republic of China.
- State Key Laboratory of Oncology in South China, Guangzhou, 510060, Guangdong, People's Republic of China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, People's Republic of China.
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Wang H, Luo C, Zhu S, Fang H, Gao Q, Ge S, Qu H, Ma Q, Ren H, Wang Y, Wang W. Serum peptidome profiling for the diagnosis of colorectal cancer: discovery and validation in two independent cohorts. Oncotarget 2017; 8:59376-59386. [PMID: 28938643 PMCID: PMC5601739 DOI: 10.18632/oncotarget.19587] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 06/29/2017] [Indexed: 01/05/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were identified as candidate biomarkers for CRC. A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort. Peptide peaks at m/z 1895.3, 2020.9 and 3238.5 were identified as the partial sequences of complement component 4 (C4), complement component 3 (C3) and fibrinogen α chain (FGA), respectively. This study potentiated peptidomic analysis as a promising in vitro diagnostic tool for diagnosis of CRC. The identified peptides suggest the involvement of the C3, C4 and FGA in CRC pathogenesis.
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Affiliation(s)
- Hao Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
| | - Chenghua Luo
- Department of Retroperitoneal Tumors Surgery, Peking University International Hospital, Beijing 102206, China
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing 100069, China.,National Center for Clinical Medical Research of Digestive Diseases, Beijing 100069, China
| | - Honghong Fang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
| | - Qing Gao
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
| | - Siqi Ge
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China.,School of Medical and Health Sciences, Edith Cowan University, Perth 6027, Australia
| | - Haixia Qu
- Bioyong (Beijing) Technology Co., Ltd., Beijing 100085, China
| | - Qingwei Ma
- Bioyong (Beijing) Technology Co., Ltd., Beijing 100085, China
| | - Hongwei Ren
- School of Life Sciences, Peking University, Beijing 100871, China
| | - Youxin Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
| | - Wei Wang
- Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China.,School of Medical and Health Sciences, Edith Cowan University, Perth 6027, Australia
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