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Zhang X, Li W, Wang X, Lin J, Dang C, Diao D. Effectiveness of D-dimer in predicting distant metastasis in colorectal cancer. PLoS One 2024; 19:e0306909. [PMID: 38995895 PMCID: PMC11244829 DOI: 10.1371/journal.pone.0306909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 06/25/2024] [Indexed: 07/14/2024] Open
Abstract
PURPOSE Patients with cancer often present with a hypercoagulable state, which is closely associated with tumor progression. The purpose of this study was to assess the diagnostic efficacy of D-dimer in predicting distant metastasis in colorectal cancer (CRC). METHODS This study included 529 patients diagnosed with CRC at our hospital between January 2020 and December 2022. Plasma coagulation indicators and tumor markers were collected prior to treatment and their diagnostic efficacy for predicting CRC metastasis was assessed by receiver operating characteristic (ROC) curves. Independent risk factors for evaluating tumor metastasis were obtained by multivariate logistic regression analysis. RESULTS The level of D-dimer in the metastatic group was significantly higher than that in the non-metastatic group (P<0.001). The results of the multiple logistic regression analysis indicated that lower level of prealbumin and platelet, and higher level of glucose, CEA and D-dimer were independent risk factors for distant metastasis in patients with CRC (P<0.05, respectively). The combination of prealbumin, glucose, D-dimer, platelet and tumor markers (PRE2) was found to be significantly more effective in predicting metastasis of CRC when compared to the combination of tumor marker alone (PRE1, P<0.001). CONCLUSION Plasma D-dimer may be a novel tumor marker for screening metastases of CRC.
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Affiliation(s)
- Xin Zhang
- Department of Oncology Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Wenxing Li
- Department of Radiotherapy, Oncology Department, The First Affiliated Hospital of Xi 'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xuan Wang
- Department of Oncology Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jinhe Lin
- Department of Oncology Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Chengxue Dang
- Department of Oncology Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Dongmei Diao
- Department of Oncology Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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Tayal D, Jain P, Goswami B. D-dimer - a multifaceted molecule. Horm Mol Biol Clin Investig 2024; 45:75-84. [PMID: 38716869 DOI: 10.1515/hmbci-2022-0093] [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: 10/11/2022] [Accepted: 04/19/2024] [Indexed: 06/27/2024]
Abstract
D-dimer, a universally unique marker for fibrin degradation, is generated through the enzymatic interplay of thrombin, factor XIIIa, and plasmin. The emergence of D-dimer-containing fibrin molecules occurs in both intravascular and extravascular spaces during pivotal physiological processes like haemostasis, thrombosis, and tissue repair. Given the inherently physiological nature of fibrin formation and fibrinolysis, basal levels of D-dimer fragments are present in plasma. Beyond its role as a marker of routine physiological processes, aberrations in D-dimer levels are indicative of a spectrum of conditions, both non-pathological and pathological. The clinical utility of D-dimer has been firmly established, particularly in scenarios like venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). Additionally, recent applications have extended to assess the prognosis of COVID-19. While D-dimer is commonly associated with thrombotic conditions, its elevation is not confined to these conditions alone. Elevated D-dimer levels are observed across various diseases, where its significance extends beyond diagnostic indicators to prognostic implications.
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Affiliation(s)
- Devika Tayal
- Department of Biochemistry, National Institute of Tuberculosis and Respiratory Disease, New Delhi, India
| | - Prerna Jain
- Department of Biochemistry, National Institute of Tuberculosis and Respiratory Disease, New Delhi, India
| | - Binita Goswami
- Department of Biochemistry, Maulana Azad Medical College, New Delhi, India
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Long T, Zhu X, Tang D, Li H, Zhang P. Application of a nomogram from coagulation-related biomarkers and C1q and total bile acids in distinguishing advanced and early-stage lung cancer. Int J Biol Markers 2024; 39:130-140. [PMID: 38303516 DOI: 10.1177/03936155241229454] [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: 02/03/2024]
Abstract
BACKGROUND This study aimed to establish a nomogram to distinguish advanced- and early-stage lung cancer based on coagulation-related biomarkers and liver-related biomarkers. METHODS A total of 306 patients with lung cancer and 172 patients with benign pulmonary disease were enrolled. Subgroup analyses based on histologic type, clinical stage, and neoplasm metastasis status were carried out and multivariable logistic regression analysis was applied. Furthermore, a nomogram model was developed and validated with bootstrap resampling. RESULTS The concentrations of complement C1q, fibrinogen, and D-dimers, fibronectin, inorganic phosphate, and prealbumin were significantly changed in lung cancer patients compared to benign pulmonary disease patients. Multiple regression analysis based on subgroup analysis of clinical stage showed that compared with early-stage lung cancer, female (P < 0.001), asymptomatic admission (P = 0.001), and total bile acids (P = 0.011) were negatively related to advanced lung cancer, while C1q (P = 0.038), fibrinogen (P < 0.001), and D-dimers (P = 0.001) were positively related. A nomogram model based on gender, symptom, and the levels of total bile acids, C1q, fibrinogen, and D-dimers was constructed for distinguishing advanced lung cancer and early-stage lung cancer, with an area under the receiver operating characteristic curve of 0.919. The calibration curve for this nomogram revealed good predictive accuracy (P-Hosmer-Lemeshow = 0.697) between the predicted probability and the actual probability. CONCLUSIONS We developed a nomogram based on gender, symptom, and the levels of fibrinogen, D-dimers, total bile acids, and C1q that can individually distinguish early- and advanced-stage lung cancer.
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Affiliation(s)
- Tingting Long
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Xinyu Zhu
- Department of Clinical Laboratory, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, PR China
| | - Dongling Tang
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, PR China
| | - Huan Li
- Department of Clinical Laboratory, Jiangxi Provincial People's Hospital, The First Hospital Affiliated to Nanchang Medical College, Nanchang, PR China
| | - Pingan Zhang
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, PR China
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Lei K, Deng Z, Wang J, Wang H, Hu R, Li Y, Wang X, Xu J, You K, Liu Z. A novel nomogram based on the hematological prognosis risk scoring system can predict the overall survival of patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2023; 149:14631-14640. [PMID: 37584710 DOI: 10.1007/s00432-023-05255-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Accepted: 08/07/2023] [Indexed: 08/17/2023]
Abstract
BACKGROUND This study aimed to establish and validate a nomogram based on a hematological prognostic risk scoring system to predict the overall survival in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS Patients diagnosed with unresectable HCC undergoing transcatheter arterial chemoembolization (TACE) in 2012-2016 and 2017-2018 were included in the development set and validation set, respectively. The clinical outcome was overall survival (OS). The LASSO regression analysis was used to construct a hematological prognostic risk scoring system (HPR) by using the 18 hematological markers of patients in the development set. Combining the features of oncology on the basis of HPR to construct a nomogram for OS. In the development set and validation sets, the C-index, calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction performance of the nomogram. RESULTS Multiple markers of immunity, coagulation, liver function, and nutrition, including red blood cell distribution width-coefficient of variation (RDW-CV), platelet (PLT), aspartate transferase (AST), alkaline phosphatase (ALP), prognostic nutritional index (PNI), and fibrinogen (Fib), construct the HPR. HPR was an independent risk factor for OS in patients with HCC. The C-index of the nomogram was 0.731 (95% confidence interval (CI) 0.712-0.749) and 0.696 (95% CI 0.668-0.725) in the development set and the validation set, respectively. CONCLUSIONS HPR was a complement to the clinical features of patients with unresectable HCC. The nomogram based on HPR proved to be a practical and effective method for prognosticating HCC patients who undergo TACE.
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Affiliation(s)
- Kai Lei
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Zhuofan Deng
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Jiaguo Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Hongxiang Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Run Hu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Yin Li
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Xingxing Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Jie Xu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Ke You
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China
| | - Zuojin Liu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400000, China.
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Mohammed HA, Ewees MG, Mahmoud NI, Ali HM, Amin E, Abdel-Bakky MS. Involvement of PI3K/HIF-1α/c-MYC/iNOS Pathway in the Anticancer Effect of Suaeda vermiculata in Rats. Pharmaceuticals (Basel) 2023; 16:1470. [PMID: 37895941 PMCID: PMC10609837 DOI: 10.3390/ph16101470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/03/2023] [Accepted: 10/08/2023] [Indexed: 10/29/2023] Open
Abstract
Suaeda vermiculata Forssk. ex JF Gmel. (SV), a traditional known plant, has shown in vitro cytotoxic activity against HepG2 and HepG-2/ADR (doxorubicin-resistant cells) liver cell carcinoma cell lines, as well as hepatoprotection against paracetamol and carbon tetrachloride (CCl4)-induced liver injury. The current study evaluated the protective effect of SV, administered against N-diethylnitrosamine (NDEA)-induced HCC in rats. The possible modulatory effect of SV on the PI3K/HIF-1α/c-MYC/iNOS pathway was investigated. Sixty male adult albino rats (200 ± 10 g) were equally classified into five groups. Group I served as a control; Group 2 (SV control group) received SV (p.o., 200 mg/kg body weight); Group 3 (NDEA-administered rats) received freshly prepared NDEA solution (100 mg/L); and Groups 4 and 5 received simultaneously, for 16 weeks, NDEA + SV extract (100 and 200 mg/kg, orally). NDEA-treated rats displayed significant increases in serum levels of AFP, CEA, PI3K, malondialdehyde (MDA), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGFR), with increased liver tissue protein expression of fibrinogen concomitant and significantly decreased concentrations of antioxidant parameters (catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH)) in comparison to normal rats. On the flip side, AFP, CEA, PI3K, MDA, EGFR, and VEGFR serum levels were significantly reduced in rats that received NDEA with SV, both at low (SV LD) and high (SV HD) doses, accompanied by significant improvements in antioxidant parameters compared to the NDEA-treated group. Conclusions: SV possesses a significant hepatoprotective effect against NDEA-induced HCC via inhibiting the PI3K/HIF-1α/c-MYC/iNOS pathway, suggesting that SV could be a promising hepatocellular carcinoma treatment.
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Affiliation(s)
- Hamdoon A. Mohammed
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia;
- Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt
| | - Mohamed G. Ewees
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 11787, Egypt; (M.G.E.); (N.I.M.)
| | - Nesreen I. Mahmoud
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 11787, Egypt; (M.G.E.); (N.I.M.)
| | - Hussein M. Ali
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia;
- Department of Biochemistry, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt
| | - Elham Amin
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia;
- Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt
| | - Mohamed S. Abdel-Bakky
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia;
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt
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Duan Y, Hou X, Guo J, Li H, Cai L, Cheng L, Zhao W, Shao X, Du H, Diao Z, Li C. D-dimer for assessment of treatment response, and survival to drug-eluting beads transarterial chemoembolization in hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2023; 47:102096. [PMID: 36801385 DOI: 10.1016/j.clinre.2023.102096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 02/04/2023] [Accepted: 02/14/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND D-dimer exhibits a certain prognostic value in hepatocellular carcinoma (HCC) patients who underwent hepatectomy and microwave ablation, while its value in estimating the clinical benefit of drug-eluting beads transarterial chemoembolization (DEB-TACE) remains unclear. Hence, this study aimed to investigate the correlation of D-dimer with tumor features, response and survival to DEB-TACE in HCC patients. METHODS Fifty-one HCC patients treated with DEB-TACE were recruited. Their serum samples at baseline and after DEB-TACE were collected and proposed for D-dimer detection by the immunoturbidimetry method. RESULTS Elevated D-dimer levels were related to a higher Child‒Pugh stage (P = 0.013), tumor nodule number (P = 0.031), largest tumor size (P = 0.004), and portal vein invasion (P = 0.050) in HCC patients. Then, patients were classified by the median value of D-dimer, and it was observed that patients with D-dimer >0.7 mg/L achieved a lower complete response rate (12.0% vs. 46.2%, P = 0.007) but a similar objective response rate (84.0% vs. 84.6%, P = 1.000) compared to those with D-dimer ≤0.7 mg/L. The Kaplan‒Meier curve showed that D-dimer >0.7 mg/L (vs. ≤0.7 mg/L) was related to shorter overall survival (OS) (P = 0.013). Further univariate Cox regression analyses showed that D-dimer >0.7 mg/L (vs. ≤0.7 mg/L) was related to unfavorable OS [hazard ratio (HR): 5.524, 95% confidence interval (CI): 1.209-25.229, P = 0.027], but it failed to independently estimate OS (HR: 10.303, 95%CI: 0.640-165.831, P = 0.100) in multivariate Cox regression analyses. Moreover, D-dimer was elevated during DEB-TACE therapy (P<0.001). CONCLUSION D-dimer may be helpful for monitoring prognosis to DEB-TACE therapy in HCC, while further large-scale-study validation is warranted.
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Affiliation(s)
- Youjia Duan
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Xiaopu Hou
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Jiang Guo
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China.
| | - Honglu Li
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Liang Cai
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Long Cheng
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Wenpeng Zhao
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Xihong Shao
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Hongliu Du
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Zhenying Diao
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
| | - Changqing Li
- Department of Oncology Interventional Radiology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshundong Road, Beijing 100015, China
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Qiao W, Wang Q, Mei T, Wang Q, Wang W, Zhang Y. External validation and improvement of the scoring system for predicting the prognosis in hepatocellular carcinoma after interventional therapy. Front Surg 2023; 10:1045213. [PMID: 36936655 PMCID: PMC10020369 DOI: 10.3389/fsurg.2023.1045213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 02/15/2023] [Indexed: 03/06/2023] Open
Abstract
Background Currently, locoregional therapies, such as transarterial chemoembolization (TACE) and ablation, play an important role in the treatment of Hepatocellular carcinoma (HCC). However, an easy-to-use scoring system that predicts recurrence to guide individualized management of HCC with varying risks of recurrence remains an unmet need. Methods A total of 483 eligible HCC patients treated by TACE combined with ablation from January 1, 2017, to December 31, 2019, were included in the temporal external validation cohort and then used to explore possibilities for refinement of the original scoring system. We investigated the prognostic value of baseline variables on recurrence-free survival (RFS) using a Cox model and developed the easily applicable YA score. The performances of the original scoring system and YA score were assessed according to discrimination (area under the receiver operating curve [AUROC] and Harrell's concordance index [C-statistic]), calibration (calibration curves), and clinical utility [decision curve analysis (DCA) curves]. Finally, improvement in the ability to predict in the different scoring systems was assessed using the Net Reclassification Index (NRI). The YA score was lastly compared with other prognostic scores. Results During the median follow-up period of 35.6 months, 292 patients experienced recurrence. In the validation cohort, the original scoring system exhibited high discrimination (C-statistic: 0.695) and calibration for predicting the prognosis in HCC. To improve the prediction performance, the independent predictors of RFS, including gender, alpha-fetoprotein (AFP) and des-γ-carboxyprothrombin (DCP), tumor number, tumor size, albumin-to-prealbumin ratio (APR), and fibrinogen, were incorporated into the YA score, an improved score. Compared to the original scoring system, the YA score has better discrimination (c-statistic: 0.712VS0.695), with outstanding calibration and the clinical net benefit, both in the training and validation cohorts. Moreover, the YA score accurately stratified patients with HCC into low-, intermediate- and high-risk groups of recurrence and mortality and outperformed other prognostic scores. Conclusion YA score is associated with recurrence and survival in early- and middle-stage HCC patients receiving local treatment. Such score would be valuable in guiding the monitoring of follow-up and the design of adjuvant treatment trials, providing highly informative data for clinical management decisions.
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Affiliation(s)
- Wenying Qiao
- Interventional Therapy Center for Oncology, Beijing You ‘an Hospital, Capital Medical University, Beijing, China
- Center for Infectious Diseases, Beijing You ‘an Hospital, Capital Medical University, Beijing, China
| | - Qi Wang
- Interventional Therapy Center for Oncology, Beijing You ‘an Hospital, Capital Medical University, Beijing, China
| | - Tingting Mei
- Interventional Therapy Center for Oncology, Beijing You ‘an Hospital, Capital Medical University, Beijing, China
| | - Qi Wang
- Center for Infectious Diseases, Beijing You ‘an Hospital, Capital Medical University, Beijing, China
| | - Wen Wang
- Center for Infectious Diseases, Beijing You ‘an Hospital, Capital Medical University, Beijing, China
- Correspondence: Wen Wang Yonghong Zhang
| | - Yonghong Zhang
- Interventional Therapy Center for Oncology, Beijing You ‘an Hospital, Capital Medical University, Beijing, China
- Correspondence: Wen Wang Yonghong Zhang
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Duan S, Zhang Y, Xu S, Jiang P, Qi Q. Contrast-Enhanced Ultrasound Parameters and D-Dimer: New Prognostic Parameters for Diffuse Large B-Cell Lymphoma. Cancer Manag Res 2022; 14:2535-2544. [PMID: 36051181 PMCID: PMC9426867 DOI: 10.2147/cmar.s326173] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 09/05/2021] [Indexed: 11/23/2022] Open
Abstract
Objective To investigate the predictive role of contrast-enhanced ultrasonography (CEUS) plus D-dimer levels in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Methods CEUS was applied to assess lymph nodes in 186 patients with confirmed DLBCL. The clinical data and laboratory indicators were collected from these patients, and a retrospective analysis was conducted on the relationship between the quantitative parameters of CEUS (TTP, PI, AUC, WOT), D-dimer levels, and clinical features of the DLBCL patients. The Cox regression model was used for univariate and multivariate analyses for the risk factors associated with the prognosis. Results There was an increase of D-dimer levels in advanced DLBCL patients, who were combined with a significant reduction in TTP and WOT and a significant increase in PI and AUC. D-dimer levels and quantitative parameters of CEUS were strongly correlated with the Ann Arbor, B symptoms, International Prognostic Index (IPI), LDH and CRP levels. The results of the Cox regression model indicated that D-dimer levels, TTP and PI, the quantitative parameters of CEUS, were important prognostic factors for DLBCL. Conclusion CEUS results and D-dimer levels can be used as independent prognostic factors for DLBCL.
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Affiliation(s)
- Shaobo Duan
- Department of Health Management, Henan Provincial People’s Hospital Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China
| | - Ye Zhang
- Department of Health Management, Henan Provincial People’s Hospital Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China
| | - Shuang Xu
- Department of Health Management, Henan Provincial People’s Hospital Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China
| | - Pei Jiang
- Department of Health Management, Henan Provincial People’s Hospital Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China
| | - Qinghua Qi
- Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China
- Correspondence: Qinghua Qi, Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China, Email
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9
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Peng F, Yuan H, Zhou YF, Wu SX, Long ZY, Peng YM. Diagnostic Value of Combined Detection via Protein Induced by Vitamin K Absence or Antagonist II, Alpha-Fetoprotein, and D-Dimer in Hepatitis B Virus-Related Hepatocellular Carcinoma. Int J Gen Med 2022; 15:5763-5773. [PMID: 35770053 PMCID: PMC9236167 DOI: 10.2147/ijgm.s362359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 06/15/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose We aimed to explore the clinical diagnostic value of combined detection via protein induced by vitamin K absence or antagonist II (PIVKA-II), alpha-fetoprotein (AFP), and D-dimer (D-D) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Materials and Methods We analyzed PIVKA-II, AFP, and D-D levels in 291 subjects comprising liver cirrhosis (LC) patients (n = 143) and HCC patients (n = 148). Receiver operating characteristic (ROC) curves were used to analyze and compare the clinical diagnostic value of the three biomarkers for HBV-related HCC alone and in combination. Results The levels of PIVKA-II, AFP, and D-D were positively correlated with tumor size in HCC patients. The levels of PIVKA-II and AFP in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients were higher than those in LC patients, while the levels of D-D were lower. The area under the curve for combined detection was greater than that for single-index detection in early-stage HCC, advanced HCC, HBV DNA+ HCC, and HBV DNA- HCC patients. Conclusion D-D may be a useful biomarker for the diagnosis of HBV-related HCC. The combined detection of PIVKA-II, AFP, and D-D had better diagnostic value for different types of HCC than the detection of individual biomarkers.
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Affiliation(s)
- Fang Peng
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
| | - Hao Yuan
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
- Correspondence: Hao Yuan, Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China, Tel +8613677366519, Email
| | - Yi-Feng Zhou
- Operating Room, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
| | - Si-Xian Wu
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
| | - Zhen-Yi Long
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
| | - Ya-Meng Peng
- Department of Clinical Laboratory, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People’s Republic of China
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Zhang LP, Ren H, Du YX, Zheng XH, Zhang ZM, Wang CF. Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection. World J Gastrointest Surg 2021; 13:279-302. [PMID: 33796216 PMCID: PMC7993003 DOI: 10.4240/wjgs.v13.i3.279] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/01/2021] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies.
AIM To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection.
METHODS We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values.
RESULTS The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection.
CONCLUSION Preoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.
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Affiliation(s)
- Li-Peng Zhang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hu Ren
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yong-Xing Du
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiao-Hao Zheng
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zong-Ming Zhang
- Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing 100073, China
| | - Cheng-Feng Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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11
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Liang YJ, Mei XY, Zeng B, Zhang SE, Yang L, Lao XM, Liao GQ. Prognostic role of preoperative D-dimer, fibrinogen and platelet levels in patients with oral squamous cell carcinoma. BMC Cancer 2021; 21:122. [PMID: 33546637 PMCID: PMC7863521 DOI: 10.1186/s12885-021-07841-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 01/26/2021] [Indexed: 12/20/2022] Open
Abstract
Background The relationship between cancer and coagulation has been intensively studied in recent years; however, the effects of coagulation factors on oral squamous cell carcinoma (OSCC) have rarely been reported. This study aimed to investigate the relationship between preoperative D-dimer (DD), fibrinogen (FIB), platelets (PLT) and OSCC, as well as the prognostic value of DD, FIB and PLT in OSCC. Methods We retrospectively investigated a total of 202 patients with OSCC treated at Guanghua Hospital of Stomatology, Sun Yat-sen University. Baseline demographic and clinicopathological information as well as both preoperative and postoperative DD, FIB and PLT results were collected from each patient, and patients with primary OSCC were followed up for disease progression, death or the end of the study. The correlations between preoperative DD, FIB, PLT and other clinical features, as well as the therapeutic effect and PFS were analysed statistically, and postoperative DD and surgical parameters were also analysed. Results Preoperative DD was significantly correlated with T stage, N stage, clinical stage and relapse of OSCC (P = 0.000, 0.001, 0.000 and 0.000, respectively). Univariate Cox regression analyses showed that high preoperative DD predicted poor prognosis in patients with OSCC (HR = 2.1, P = 0.033), while FIB and PLT showed no prognostic values. Postoperative DD was significantly correlated with preoperative DD and surgical type but not the duration of surgery (P = 0.005, 0.001 and 0.244, respectively). Conclusion In this study, we suggested that high preoperative DD level may serve as an indicator for synchronous neck dissection in patients with T1, 2 OSCC, and the elevated DD level might be the marker of disease progression in patient follow up. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-07841-5.
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Affiliation(s)
- Yu-Jie Liang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Xue-Ying Mei
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Bin Zeng
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Si-En Zhang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Le Yang
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Xiao-Mei Lao
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China. .,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China.
| | - Gui-Qing Liao
- Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, Guangdong, China.,Guangdong Provincial Key Laboratory of Stomatology, No. 74, 2nd Zhongshan Road, Guangzhou, 510080, Guangdong, China
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12
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Wang H, Xiang Y, Li X, Liu S, Liu L. High lymphocyte‑to‑monocyte ratio is associated with low α‑fetoprotein expression in patients with hepatitis B virus‑associated hepatocellular carcinoma. Mol Med Rep 2020; 22:2673-2684. [PMID: 32945410 PMCID: PMC7453599 DOI: 10.3892/mmr.2020.11387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 05/28/2020] [Indexed: 11/09/2022] Open
Abstract
The association of the peripheral lymphocyte‑to‑monocyte ratio (LMR) with α‑fetoprotein (AFP) status in patients with AFP‑positive and AFP‑negative hepatocellular carcinoma (HCC) has not been investigated in detail. The aim of the present study was to examine the association between the LMR and AFP status in these patients. The samples were obtained from patients with a hepatitis B virus (HBV) infection, who were negative for non‑HBV hepatitis viruses and who did not suffer from autoimmune hepatitis. These patients were retrospectively reviewed and the differences of test indicators in the AFP‑negative and AFP‑positive groups were assessed. Flow cytometry was used to detect the expression levels of CD4, CD8 and programmed cell death protein 1 (PD‑1), and ELISAs were used to analyze the expression levels of interleukin (IL)‑10 and transforming growth factor (TGF)‑β1. In addition, luciferase reporter assays were used to assess binding of the IL‑10 promoter to the glucocorticoid receptor (GR) gene. Receiver operating characteristic curve and Spearman correlation analyses demonstrated that the AFP‑negative HCC group exhibited a higher LMR, lower D‑dimer and lower fibrin degradation products compared with the AFP‑positive HCC group. The cut‑off value of the LMR was 2.01 for AFP detection, with a sensitivity of 68.6% and a specificity of 75%. The high LMR noted in the AFP‑negative HCC group was accompanied by a lower proportion of CD4+ T lymphocytes and CD8‑PD‑1 expression compared with the corresponding levels of these parameters in the AFP‑positive HCC group. Furthermore, the high levels of IL‑10 and low levels of TGF‑β1 were expressed in the AFP‑positive HCC group. The data indicated that the IL‑10‑592 promoter exhibited a potent induction of luciferase activity in 293T cells cotransfected with a GR‑overexpressing vector compared with the control cells. However, the relative luciferase activity was not altered following a mutation or polymorphism in the IL‑10 gene. These results suggested that a high LMR was indicative of low AFP expression in HBV‑associated HCC patients.
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Affiliation(s)
- Haixia Wang
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
| | - Yu Xiang
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
| | - Xinyu Li
- Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Shuang Liu
- Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Linxiu Liu
- Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China
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13
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Dai T, Peng L, Lin G, Li Y, Yao J, Deng Y, Li H, Wang G, Liu W, Yang Y, Chen G, Wang G. Preoperative elevated plasma fibrinogen level predicts tumor recurrence and poor prognosis in patients with hepatocellular carcinoma. J Gastrointest Oncol 2019; 10:1049-1063. [PMID: 31949922 DOI: 10.21037/jgo.2019.09.11] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Elevated plasma fibrinogen has been reported to be associated with poor prognosis in several cancers. The aim of present study was to investigate the prognostic value of preoperative plasma fibrinogen in hepatocellular carcinoma (HCC) patients. Methods Data were collected retrospectively from 302 HCC patients who received hepatectomy. The association between fibrinogen and clinicopathological characteristics was evaluated. Both univariate and multivariate analyses were performed to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). And accordingly, the nomograms were constructed. Results Elevated plasma fibrinogen (>4 g/L) was correlated with larger tumor diameter, the presence of vascular invasion, lower MELD score, higher NLR, advanced Barcelona Clinic Liver Cancer stage and poor-moderate pathological differentiation. On multivariate analysis, the elevated plasma fibrinogen was found independently associated with poor DFS (HR =1.575, P=0.024) and OS (HR =2.051, P=0.025). And the nomograms including fibrinogen were constructed to predict DFS and OS for HCC patients. Both DFS and OS in patients with plasma fibrinogen >4 g/L were significantly lower than those with fibrinogen ≤4 g/L (1-, 3-, 5-year DFS: 34.2%, 19.5% and 0.0% vs. 60.4%, 34.2% and 30.2%; 1-, 3-, 5-year OS: 83.4%, 62.7% and 48.8% vs. 95.4%, 84.3% and 75.8%, both P<0.001). Besides, subgroup analyses also showed the prognostic values of fibrinogen in HCC patients with/without cirrhosis or high AFP levels, and in those with single tumor and BCLC 0-A stage. Conclusions Preoperative elevated plasma fibrinogen was an independent prognostic factor associated with poor prognosis in HCC patients receiving liver resection.
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Affiliation(s)
- Tianxing Dai
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Lingrong Peng
- Department of Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Guozhen Lin
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Yang Li
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, China
| | - Jia Yao
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, China
| | - Yinan Deng
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, China
| | - Hua Li
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, China
| | - Genshu Wang
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, China
| | - Wei Liu
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, China
| | - Guihua Chen
- Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, China.,Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Guoying Wang
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.,Organ Transplantation Institute of Sun Yat-sen University, Guangzhou 510630, China
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14
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Dong Y, Hou H, Chen A, Ma W, Yin M, Meng F, Hu C, Wang H, Cai J. Generation of a Monoclonal Antibody against D-Dimer Using HTS-Based LiCA. SLAS DISCOVERY 2019; 25:310-319. [PMID: 31560248 DOI: 10.1177/2472555219878407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
D-dimer is an essential diagnostic index of thrombotic diseases. Since the existing anti-D-dimer antibodies vary in quality and specificity, a search for alternative anti-D-dimer antibodies is required. The present study aimed to screen a novel monoclonal antibody (mAb) against D-dimer using a light-initiated chemiluminescence assay (LiCA). In this work, mice were immunized with antigen prepared from human plasma by enzyme hydrolysis. After screening, a novel mAb, DD 2G11, was obtained. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis indicated that DD 2G11 could be used as a standard marker for D-dimer. The isotype of DD 2G11 was IgG1, the Ka value was 0.646 nM-1, and the Kd value was 50 nM, indicating that the binding affinity to D-dimer was very high. Furthermore, no cross-reactivity between DD 2G11 and other fibrinogen degradation products (FgDPs) was found. Finally, the correlation between DD 2G11 and the reference antibody (commercial antibody) was investigated by analyzing 56 clinical samples using a latex-enhanced turbidimetric immunoassay (LTIA). The R2 value of the linear regression was 0.94538, indicating that DD 2G11 met clinical requirements. In conclusion, the present study provides a more expeditious protocol to screen mAbs and provides a clinically usable mAb against D-dimer.
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Affiliation(s)
- Yuan Dong
- Academy of Laboratory, Jilin Medical University, Jilin, PR China
| | - Hanjin Hou
- Academy of Laboratory, Jilin Medical University, Jilin, PR China
| | - An Chen
- Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, PR China
| | - Wei Ma
- Academy of Laboratory, Jilin Medical University, Jilin, PR China
| | - Moli Yin
- Academy of Laboratory, Jilin Medical University, Jilin, PR China
| | - Fanwei Meng
- Academy of Laboratory, Jilin Medical University, Jilin, PR China
| | - Chuanmin Hu
- Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, PR China.,Jilin Collaborative Innovation Center for Antibody Engineering, Jilin Medical University, Jilin, PR China
| | - Huiyan Wang
- Jilin Collaborative Innovation Center for Antibody Engineering, Jilin Medical University, Jilin, PR China
| | - Jianhui Cai
- Jilin Collaborative Innovation Center for Antibody Engineering, Jilin Medical University, Jilin, PR China
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15
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Rong G, Fan W, Shen J. High pretreatment plasma D-dimer levels predict poor prognosis in gastrointestinal cancers: A meta-analysis. Medicine (Baltimore) 2019; 98:e16520. [PMID: 31335729 PMCID: PMC6709134 DOI: 10.1097/md.0000000000016520] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND High pretreatment plasma D-dimer levels can predict poor prognosis in various types of gastrointestinal carcinomas. Our meta-analysis explored the correlation between plasma D-dimer levels and prognosis in gastrointestinal malignancies. METHODS Two independent reviewers conducted a comprehensive search from PubMed, ScienceDirect, Embase, Web of Science and the Cochrane Library. All articles evaluating the correlation between pretreatment plasma D-dimer levels and prognosis in gastrointestinal malignancies were searched. We chose overall survival (OS) as the primary survival outcome measure and progression-free survival (PFS), disease-free survival (DFS) and cancer-specific survival (CSS) as the secondary survival outcome measures. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) from the eligible publications. RESULTS We included 30 studies involving 5928 gastrointestinal cancer patients. There was an obvious correlation between high D-dimer levels and poor OS (HR = 2.01, 95% CI = 1.72-2.36, P < .01). High plasma D-dimer levels were correlated with shorter PFS (HR = 1.34, 95% CI = 1.05-1.70, P = .32), DFS (HR = 1.67, 95% CI = 1.12-2.50, P < .01) and CSS rates (HR = 1.93, 95% CI = 1.49-2.49, P = .66). CONCLUSIONS Elevated pretreatment plasma D-dimer levels might help predict poor prognosis in patients with gastrointestinal malignancies.
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Affiliation(s)
- Guoyi Rong
- Oncology Department, Traditional Chinese Medicine Hospital of Jiulongpo District in Chongqing
| | - Wenxin Fan
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China
| | - Jian Shen
- Oncology Department, Traditional Chinese Medicine Hospital of Jiulongpo District in Chongqing
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16
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Li T, Yu Y, Liu J, Tian X, Kong M, Wu L, Tang S, Gu S, Zhao J, Cui Y, Hu J. PIVKA-II level is correlated to development of portal vein tumor thrombus in patients with HBV-related hepatocellular carcinoma. Infect Agent Cancer 2019; 14:13. [PMID: 31114628 PMCID: PMC6515665 DOI: 10.1186/s13027-019-0229-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 04/17/2019] [Indexed: 01/28/2023] Open
Abstract
Aim To evaluate the correlation of serum PIVKA-II levels and development of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients. Methods One hundred and twenty-three patients with newly diagnosed HCC were included in this study between March 2016 and October 2018. Thirty-five of these patients were detected with PVTT and all subjects were randomly divided to analysis group (N = 73) and validation (N = 50) group. Serum levels of PIVKA-II, laboratory tests including serum aspartate aminotransferase, total bilirubin, platelet count, albumin levels were demonstrated in all the patients. T-test, chi-squared test and logistic regression was used for analyzing data. Diagnostic efficiency and cut-off value of PIVKA-II in PVTT development of HCC patients were calculated using receiver operator curve (ROC) analysis. Results Serum level of PIVKA-II in HCC patients with PVTT was significantly higher than that in HCC patients without PVTT (995.8 mAU/ml vs 94.87 mAU/ml; P = 0.003), as well as D-dimer levels (2.12 mg/L vs 0.56 mg/L P = 0.001). Univariate analysis showed that high serum D-dimer level was an independent risk factor for development of PVTT (OR = 1.22, 95%CI 1.02-1.45). ROC curve showed that among analysis group, the area under ROC curve (AUROC) of PIVKA-II was 0.73 (95%CI 0.59-0.86). For the detection of PVTT in HCC, PIVKA-II had a sensitivity of 83.7% and a specificity of 69.2% at a cutoff of 221.26 mAU/ml, which had a sensitivity of 85.71% and a specificity of 55.56% in validation group, respectively. Conclusion Serum PIVKA-II level is a potential marker for diagnosis of PVTT in HCC patients, which may guide therapeutic strategy and assessment of tumor prognosis of HCC.
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Affiliation(s)
- Tao Li
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 Shandong Province China
| | - Yuanzi Yu
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 Shandong Province China
| | - Juan Liu
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 Shandong Province China
| | - Xiangguo Tian
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 Shandong Province China
| | - Meng Kong
- Department of Gastrointestinal surgery, Provincial Hospital affiliated to Shandong University, Jing 5 Road, Jinan, People's Republic of China
| | - Lei Wu
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 Shandong Province China
| | - Shaocan Tang
- Department of rehabilitation, Provincial Hospital affiliated to Shandong University, Jing 5 Road, Jinan, People's Republic of China
| | - Shengqing Gu
- Department of Gastroenterology, Shouguang peoples' Hospital, No.45, health street, Shouguang city, Weifang city, People's Republic of China
| | - Jingfang Zhao
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 Shandong Province China
| | - Yi Cui
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 Shandong Province China
| | - Jinhua Hu
- Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, 324, Jing 5 Rd, Jinan, 250021 Shandong Province China
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Symptomatic aneurysmal bone cysts of the spine: clinical features, surgical outcomes, and prognostic factors. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2019; 28:1537-1545. [PMID: 30838451 DOI: 10.1007/s00586-019-05920-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 01/30/2019] [Accepted: 02/12/2019] [Indexed: 01/14/2023]
Abstract
PURPOSE The aim of the study was to report the long-term outcomes and analyze the potential prognostic factors that may contribute to symptomatic patients with aneurysmal bone cyst (ABC) of the spine undergoing surgical treatments. METHODS A retrospective analysis of consecutive patients with ABCs of the spine was performed. The clinical features were reviewed, and the disease-free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Factors with p values ≤ 0.05 were subjected to multivariate analysis by Cox proportional hazards model to identify the independent prognostic contributors. p values < 0.05 were considered statistically significant. RESULTS A total of 42 patients with ABCs of the spine were included in the study. All patients received surgical treatments. The mean follow-up period was 41.3 months (median 39.5, range 24-64). Local recurrence was detected in eight patients after surgery in our center, whereas death occurred in three patients. The estimated 5-year DFS and OS rate was 54.1% and 76.8%, respectively. The statistical analyses indicated that both en bloc resection and primary/secondary tumor status were independent prognostic factors for DFS. CONCLUSIONS Secondary ABC status may be associated with worse prognosis, and en bloc resection remains the treatment of choice for ABCs with neurologic deficits or spinal instability of the spine, which is correlated with better prognosis for local tumor control. These slides can be retrieved under Electronic Supplementary Material.
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Chen X, Chang Z, Liu Z. D-dimer increase: an unfavorable factor for patients with primary liver cancer treated with TACE. Cancer Chemother Pharmacol 2019; 83:797-802. [PMID: 30758650 DOI: 10.1007/s00280-019-03778-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 01/13/2019] [Indexed: 01/23/2023]
Abstract
PURPOSE To explore the clinical significance of plasma D-dimer increase for transcatheter arterial chemoembolization (TACE) in patients with primary liver cancer (PLC). METHODS The clinical data of 80 PLC patients who underwent TACE in our hospital from January 2015 to January 2017 were collected, including the plasma D-dimer level 1 week before TACE (D0), D-dimer level 1 month after TACE (D1) and D-dimer level when the disease begins to progress (D2). 1 Month after TACE, these patients were divided into two groups according to the mRecist criteria: disease-controlled group (CR + PR + SD) and disease-progressing group (PD). In all subjects, progression-free survival (PFS) was recorded. D0 and D1 were compared between the two groups by the rank sum test; and the relation between D-dimer level and PFS was assessed by the Kaplan-Meier test and Breslow test. RESULTS In the disease-controlled group, there was no significant difference between D0 and D1 (P > 0.05); in the disease-progressing group, D1 was significantly higher than D0 (P < 0.05) and the D1 is higher than that in disease-controlled group. In the patients with a negative D1 or D2, PFS was longer than those with a positive level (both P < 0.05), but such difference was not statistically significant in D0 (P > 0.05). In the patients with a D-dimer level increase after TACE (group 3), PFS was shorter than that in those with a D-dimer level decrease after TACE (Group 1) and that in those with a relatively stable D-dimer level before and after TACE (Group 2) (P < 0.05); survival in Group 1 was slightly but not significantly longer than that in Group 2 (P > 0.05). CONCLUSION The change in plasma D-dimer level can be used as a biological index to assess the efficacy of TACE and prognosis for PLC patients, and thus, a positive D-dimer level or D-dimer increase after TACE is an unfavorable factor.
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Affiliation(s)
- Xujiao Chen
- Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhihui Chang
- Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhaoyu Liu
- Shengjing Hospital of China Medical University, Shenyang, China.
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Xu K, Wan W, Li B, Li J, Huang Q, Liu Y, Jiang D, Xu Y, Xiao J. Prognostic Significance of Preoperative Plasma D-Dimer Level and Clinical Factors in Patients with Spinal Giant Cell Tumor: Retrospective Analysis of 153 Patients in a Single Center. World Neurosurg 2019; 122:e872-e880. [DOI: 10.1016/j.wneu.2018.10.169] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 10/21/2018] [Accepted: 10/23/2018] [Indexed: 12/17/2022]
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20
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Huang G, Jiang H, Lin Y, Wu Y, Cai W, Shi B, Luo Y, Jian Z, Zhou X. Prognostic value of plasma fibrinogen in hepatocellular carcinoma: a meta-analysis. Cancer Manag Res 2018; 10:5027-5041. [PMID: 30464603 PMCID: PMC6214315 DOI: 10.2147/cmar.s175780] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Elevated plasma fibrinogen levels have been associated with tumor progression in several malignancies. Our study aims to characterize the clinical significance of elevated plasma fibrinogen levels in patients with hepatocellular carcinoma (HCC). Materials and methods Relevant published articles were systematically searched in electronic databases including PubMed, Embase, and Web of Science. The pooled differences in plasma fibrinogen levels among HCC, cirrhotic, and control groups were expressed as weighted mean differences (WMDs) and their corresponding 95% CIs. The associations between elevated fibrinogen and overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS) were expressed as HRs and their 95% CIs, whereas the associations between elevated fibrinogen and various types of clinical characteristic of patients with HCC were expressed as ORs and their corresponding 95% CIs. Results Results showed that the plasma fibrinogen levels in patients with HCC were not significantly different than that in healthy controls (WMD = 0.50, 95% CI = [−0.82, 1.82], P = 0.457) or patients with cirrhosis (WMD = −0.62, 95% CI = [−1.56, 0.33], P = 0.200). However, our results showed that compared to those with normal levels, patients with HCC and elevated plasma fibrinogen levels showed poorer OS (HR = 2.08, 95% CI = [1.67, 2.59], P < 0.0001) and DFS/RFS (HR = 1.90, 95% CI = [1.52, 2.37], P < 0.0001). Results of trial sequential analysis of the OS indicated that currently available studies were sufficient to validate the negative prognostic value of elevated plasma fibrinogen in patients with HCC. Clinicopathological analyses showed that high plasma fibrinogen levels were associated with tumor progression as indicated by advanced tumor stage, larger tumor size, increased tumor number, and the presence of vascular invasion. Conclusion Elevated plasma fibrinogen levels are associated with poor prognosis and advanced tumor progression. Plasma fibrinogen may serve as a negative prognostic biomarker in patients with HCC.
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Affiliation(s)
- Guanqun Huang
- Department of General Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, People's Republic of China
| | - Hui Jiang
- Department of Abdominal Oncology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, People's Republic of China,
| | - Ye Lin
- Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, People's Republic of China,
| | - Yanpeng Wu
- Department of General Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, People's Republic of China
| | - Weilong Cai
- Department of General Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, People's Republic of China
| | - Boyun Shi
- Department of Abdominal Oncology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, People's Republic of China,
| | - Yuanwei Luo
- Department of General Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, People's Republic of China
| | - Zhixiang Jian
- Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, People's Republic of China,
| | - Xinke Zhou
- Department of Abdominal Oncology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, People's Republic of China,
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21
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Lin Y, Liu Z, Qiu Y, Zhang J, Wu H, Liang R, Chen G, Qin G, Li Y, Zou D. Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: A systematic review and meta-analysis. Eur J Surg Oncol 2018; 44:1494-1503. [DOI: 10.1016/j.ejso.2018.07.052] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 07/23/2018] [Indexed: 12/20/2022] Open
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22
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Xu K, Lou Y, Sun R, Liu Y, Li B, Li J, Huang Q, Wan W, Xiao J. Establishment of a Nomogram-Based Model for Predicting the Prognostic Value of Inflammatory Biomarkers and Preoperative D-Dimer Level in Spinal Ewing's Sarcoma Family Tumors: A Retrospective Study of 83 Patients. World Neurosurg 2018; 121:e104-e112. [PMID: 30218803 DOI: 10.1016/j.wneu.2018.09.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 09/01/2018] [Accepted: 09/04/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Ewing's sarcoma family tumors (ESFTs) are the second most common malignancy in children and adolescents. The purpose of the present retrospective study was to evaluate the prognostic role of inflammatory biomarkers and preoperative D-dimer levels in patients with spinal ESFTs. METHODS The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, albumin/globulin ratio, C-reactive protein/albumin ratio (CAR), preoperative D-dimer level, and clinical parameters were evaluated and analyzed. Univariate and multivariate analyses for disease-free survival (DFS) and overall survival (OS) were performed using the log-rank test and Cox regression analysis, respectively. The DFS and OS rates were calculated using the Kaplan-Meier method. Nomograms were established to predict DFS and OS quantitatively. RESULTS The optimal cutoff values for D-dimer, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, CAR, and albumin/globulin ratio were 0.3, 3.2, 168, 2.2, 1.5, and 1.4, respectively. The patients were stratified into 2 groups according to the cutoff values. Multivariate analysis revealed that age, resection mode, and D-dimer level were favorable prognostic factors for DFS and OS (P < 0.05). Metastasis and CAR <1.5 were significantly associated with OS (P < 0.05). Nomograms with all significant factors were established to predict DFS and OS. CONCLUSIONS Our results have indicated that the preoperative D-dimer level is an effective prognostic factor with discriminatory ability for DFS and OS, superior to other indicators. Also, CAR was favorable prognostic factor for OS. Nomograms of DFS and OS can be recommended as practical models to evaluate the prognosis for patients with spinal ESFTs.
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Affiliation(s)
- Kehan Xu
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Huangpu District, Shanghai, People's Republic of China
| | - Yan Lou
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Huangpu District, Shanghai, People's Republic of China
| | - Rui Sun
- Department of Neurology, Jinling Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China
| | - Yujie Liu
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Huangpu District, Shanghai, People's Republic of China
| | - Bo Li
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Huangpu District, Shanghai, People's Republic of China
| | - Jialin Li
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Huangpu District, Shanghai, People's Republic of China
| | - Quan Huang
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Huangpu District, Shanghai, People's Republic of China
| | - Wei Wan
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Huangpu District, Shanghai, People's Republic of China
| | - Jianru Xiao
- Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Huangpu District, Shanghai, People's Republic of China.
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23
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Liu Z, Ye Q, Wu L, Gao F, Xie H, Zhou L, Zheng S, Xu X. Metallothionein 1 family profiling identifies MT1X as a tumor suppressor involved in the progression and metastastatic capacity of hepatocellular carcinoma. Mol Carcinog 2018; 57:1435-1444. [PMID: 29873415 DOI: 10.1002/mc.22846] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2017] [Revised: 05/14/2018] [Accepted: 06/01/2018] [Indexed: 12/20/2022]
Abstract
Metallothionein 1 (MT1s) is a family of cysteine-rich proteins with diverse functions such as metal homeostasis, oxidative stress, and carcinogenesis. However, its involvement in hepatocellular carcinoma (HCC) remains not fully understood. We aimed to explore the contribution of the individual member of MT1s to HCC. Its member mRNA levels were determined in cohort 1 of normal (n = 30), cirrhotic (n = 30), peritumoral (n = 135), and HCC (n = 135). In cohort 1, seven of eight members were down-regulated during the transition from normal liver to HCC, and only MT1G and MT1X were correlated with tumor features and outcomes. The MT1X was selected to be further stained in cohort 2 consisting of a series of liver nodules (15 normal livers, 33 cirrhotic livers, 12 dysplastic nodules, 31 HCC, and 9 HCC metastasis), and in cohort 3 (HCC, n = 85). In cohort 2, MT1X immunoreactivity was reduced in HCC and lost in metastatic HCC and showed good diagnostic performance for HCC (AUC = 0.754, 95%IC = 0.659-0.849). In cohort 3, MT1X expression in peritumoral tissues was independent predictor for HCC (recurrence free survival: HR = 0.34, 95%CI = 0.17-0.66; overall survival: HR = 0.32, 95%CI = 0.16-0.60). Moreover, we found that ectopic overexpression of MT1X delayed G1/S progression of cell cycle and promoted apoptosis in HCC cells in vitro, and suppressed tumor growth and lung metastasis in nude mice in vivo. We further demonstrated that MT1X induces cell cycle arrest and apoptosis by inactivating NF-κB signaling in HCC. In conclusion, MT1X may serve as a candidate of prognostic indicator and inhibits the progression and metastasis of HCC.
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Affiliation(s)
- Zhikun Liu
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Public Health, Hangzhou, China
| | - Qianwei Ye
- Key Lab of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Public Health, Hangzhou, China
| | - Lingjiao Wu
- Key Lab of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Public Health, Hangzhou, China
| | - Feng Gao
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Public Health, Hangzhou, China
| | - Haiyang Xie
- Key Lab of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Public Health, Hangzhou, China
| | - Lin Zhou
- Key Lab of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Public Health, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Public Health, Hangzhou, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Lab of Combined Multi-Organ Transplantation, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Public Health, Hangzhou, China
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24
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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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25
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Ji R, Ren Q, Bai S, Wang Y, Zhou Y. Prognostic significance of pretreatment plasma fibrinogen in patients with hepatocellular and pancreatic carcinomas: A meta-analysis. Medicine (Baltimore) 2018; 97:e10824. [PMID: 29923974 PMCID: PMC6023750 DOI: 10.1097/md.0000000000010824] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Accepted: 04/25/2018] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The high pretreatment plasma fibrinogen has been widely reported to be a possible biomarker for predicting prognosis in hepatocellular carcinoma (HCC) and pancreatic carcinoma (PC), but persuasive conclusion has not been made yet. Thus, we herein conducted a meta-analysis to comprehensively assess the prognostic value of high pretreatment plasma fibrinogen in patients with HCC and PC. METHOD We systematically searched PubMed, EMBASE, and Web of Science to identify eligible studies from inception to November 10, 2017. RESULTS Finally, a total of 12 publications with 13 studies were included. Of these eligible studies, 5 publications with 6 studies were about pancreatic cancer and 7 were about HCC. The pooled analysis indicated that high plasm fibrinogen level was significantly related to worse overall survival (OS) in HCC [hazard ratio (HR) = 1.87; 95% confidence interval (CI): 1.55-2.24; P < .01]. Similarly, from our result, it was found that high plasm fibrinogen was also significantly associated with worse OS in PC (HR = 1.56; 95% CI: 1.13-2.15; P < .01). CONCLUSION Taken together, our meta-analysis confirmed that high plasma fibrinogen level could predict worse survival in HCC and PC.
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Affiliation(s)
- Rui Ji
- Department of Gastroenterology, the First Hospital of Lanzhou University
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Qian Ren
- Department of Gastroenterology, the First Hospital of Lanzhou University
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Suyang Bai
- Department of Gastroenterology, the First Hospital of Lanzhou University
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yuping Wang
- Department of Gastroenterology, the First Hospital of Lanzhou University
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yongning Zhou
- Department of Gastroenterology, the First Hospital of Lanzhou University
- Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China
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26
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Yan C, Yang Q, Gong Z. Activation of Hepatic Stellate Cells During Liver Carcinogenesis Requires Fibrinogen/Integrin αvβ5 in Zebrafish. Neoplasia 2018; 20:533-542. [PMID: 29649779 PMCID: PMC5915969 DOI: 10.1016/j.neo.2018.02.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 02/07/2018] [Accepted: 02/14/2018] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and it usually develops from a background of liver fibrosis or inflammation. The crosstalk between tumor cells and stromal cells plays an important and stimulating role during tumor progression. Previously we found in a krasV12-induced zebrafish HCC model that oncogenic hepatocytes activate hepatic stellate cells (HSCs) by up-regulation of serotonin and activate neutrophils and macrophages by up-regulation of cortisol. In the present study, we found a novel signaling transduction mechanism between oncogenic hepatocytes and HSCs. After krasV12 induction, fibrinogen was up-regulated in oncogenic hepatocytes. We reasoned that fibrinogen may bind to integrin αvβ5 on HSCs to activate HSCs. Consistent with this notion, pharmaceutical treatment using an antagonist of integrin αvβ5, cilengitide, significantly blocked HSC activation and function, accompanied by attenuated proliferation of oncogenic hepatocytes and progression of liver fibrosis. On the contrary, adenosine 5'-diphosphate, an agonist of αvβ5, activated HSCs significantly that further stimulated the tumor progression and liver fibrosis. Interestingly, in human liver disease samples, we detected an increased level of fibrinogen during tumor progression which indicated the potential role of fibrinogen signaling in HCC progression. Thus, we concluded a novel interaction between oncogenic hepatocytes and HSCs through the fibrinogen related pathway in both the zebrafish HCC model and human liver disease samples.
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Key Words
- a-sma, alpha-smooth muscle actin
- dox, doxycycline
- dpf, day post fertilization
- dpi, day post induction
- facs, fluorescence-activated cell sorting
- gfap, glial fibrillary acidic protein
- h&e, hematoxylin and eosin
- hcc, hepatocellular carcinoma
- hsc, hepatic stellate cell
- if, immunofluorescence
- ihc, immunohistochemistry
- oh, oncogenic hepatocyte
- tme, tumor microenvironment
- wt, wild type
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Affiliation(s)
- Chuan Yan
- Department of Biological Sciences, National University of Singapore, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
| | - Qiqi Yang
- Department of Biological Sciences, National University of Singapore, Singapore
| | - Zhiyuan Gong
- Department of Biological Sciences, National University of Singapore, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
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