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Li TH, Sun X, Li CG, Yin YP, Tao KX. Hypercoagulation after neoadjuvant immunochemotherapy as a new prognostic indicator in patients with locally advanced gastric cancer undergoing surgery. World J Gastrointest Oncol 2025; 17:100927. [PMID: 40092957 PMCID: PMC11866221 DOI: 10.4251/wjgo.v17.i3.100927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/06/2024] [Accepted: 12/25/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Coagulation status is closely related to the progression of malignant tumors. In the era of neoadjuvant immunochemotherapy (NICT), the prognostic utility of coagulation indicators in patients with locally advanced gastric cancer (LAGC) undergoing new treatments remains to be determined. AIM To determine whether hypercoagulation is an effective prognostic indicator in patients with LAGC who underwent radical resection after NICT. METHODS A retrospective analysis of clinical data from 104 patients with LAGC, who underwent radical resection after NICT between 2020 and 2023, was performed. D-dimer and fibrinogen concentrations were measured one week before NICT, and again one week before surgery, to analyze the association between these two indicators and their combined indices [non-hypercoagulation (D-dimer and fibrinogen concentrations within the upper limit of normal) vs hypercoagulation (D-dimer or fibrinogen concentrations above the upper limit of normal)] with prognosis. After radical resection, patients were followed-up periodically. The median follow-up duration was 21 months. RESULTS Data collected after NICT revealed that the three-year overall survival (OS) and disease-free survival (DFS) rates the non-hypercoagulation group were significantly better than those in the hypercoagulation group [94.4% vs 78.0% (P = 0.019) and 87.0% vs 68.0% (P = 0.027), respectively]. Multivariate analysis indicated that hypercoagulation after NICT was an independent factor for poor postoperative OS [hazard ratio (HR) 4.436, P = 0.023] and DFS (HR 2.551, P = 0.039). Pre-NICT data demonstrated no statistically significant difference in three-year OS between the non-hypercoagulation and hypercoagulation groups (88.3% vs 84.1%, respectively; P = 0.443). CONCLUSION Hypercoagulation after NICT is an effective prognostic indicator in patients with LAGC undergoing radical gastrectomy.
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Affiliation(s)
- Tian-Hao Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xiong Sun
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Cheng-Guo Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Yu-Ping Yin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Kai-Xiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Wu B, Zhang G, Zhao X, Wang J, Wang D, Zhang Y, Yu M, Cai H. Association between D-dimer levels and clinicopathological characteristics of pancreatic cancer and its role in prognosis: A systematic review and meta-analysis. Asian J Surg 2024; 47:3417-3424. [PMID: 38453610 DOI: 10.1016/j.asjsur.2024.02.043] [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: 09/05/2023] [Revised: 01/23/2024] [Accepted: 02/02/2024] [Indexed: 03/09/2024] Open
Abstract
According to previous studies, D-dimer levels are associated with the prognosis of patients with pancreatic cancer (PC). However, the results of current studies are limited and controversial. Therefore, we performed this meta-analysis to assess the relationship between D-dimer levels and prognostic and pathological characteristics of PC patients. We first searched the databases of PubMed, Embase, The Cochrane Library, Web Of Science, CBM, VIP, CNKI and Wanfang to identify available studies. The relationship between pretreatment d-dimer levels and prognosis in PC patients was assessed using the combined hazard ratio (HR) and 95% confidence interval (CI). The combined odds ratio (OR) and 95% confidence interval (CI) were used in assessing the relationship between pathological characteristics and d-dimer levels in PC patients. Stata 12.0 software was used for all statistical analyses. In total, we included 13 studies involving 2777 patients. The results showed that elevated pre-treatment d -dimer levels were significantly associated with OS deterioration (HR = 1.46 95% CI: 1.34-1.59; p < 0.001). We also performed subgroup analyses based on sample size, d -dimer threshold, follow-up time, and HR source to further validate the prognostic value of pretreatment d -dimer levels in PC. In addition, according to the analysis, high pretreatment d -dimer levels in PC patients were associated with late tumor stage (OR = 4.78, 95% CI 1.73-13.20, p < 0. 005), larger tumor size (OR = 1.72, 95% CI 1.25-2.35, p < 0.005), and distant metastasis of tumor (OR = 5.06, 95% CI 2.45-10.43, p < 0.005) were significantly associated. In contrast, other clinicopathological factors, including age, gender and lymph node metastasis, were not associated with d-dimer levels. In conclusion, we found that high pre-treatment d-dimer levels were associated with a poor prognosis in PC patients, in relation to later tumor stage, larger tumor size and the development of distant metastases. Plasma d-dimer levels can be used as a biomarker of prognosis in PC patients.
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Affiliation(s)
- Bin Wu
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, 730000, China
| | - Guangming Zhang
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, 730000, China; The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, China
| | - Xiashuang Zhao
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, 730000, China
| | - Jie Wang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, 730000, China
| | - Da Wang
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, 730000, China; Jiangsu University, Zhenjiang, 212000, China
| | - Yipeng Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, 730000, China
| | - Miao Yu
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, 730000, China; Gansu Provincial Hospital, Lanzhou, 730000, China
| | - Hui Cai
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, 730000, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, 730000, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, 730000, China; Gansu Provincial Hospital, Lanzhou, 730000, China; The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, China.
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3
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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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Sugiyama F, Kanda M, Shimizu D, Umeda S, Inokawa Y, Hattori N, Hayashi M, Tanaka C, Nakayama G, Kodera Y. Absence of Hypercoagulation Status after Neoadjuvant Treatment is Associated with Favorable Prognosis in Patients Undergoing Subtotal Esophagectomy for Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2024; 31:3417-3425. [PMID: 38245650 DOI: 10.1245/s10434-024-14938-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 12/29/2023] [Indexed: 01/22/2024]
Abstract
BACKGROUND Abnormal activation of the coagulation system is associated with malignant tumor progression. Although neoadjuvant treatment (NAT) for resectable esophageal squamous cell carcinoma (ESCC) is the standard of care, the correlation between coagulation status and prognosis of patients undergoing preoperative treatment is insufficiently understood. METHODS Patients (n = 200) who underwent radical subtotal esophagectomy after preoperative treatment for ESCC between January 2012 and December 2021were included in the analysis. Plasma D-dimer and fibrinogen levels and their combined indices (non-hypercoagulation; D-dimer and fibrinogen levels within the upper normal limit, or hypercoagulation; D-dimer or fibrinogen levels above the upper normal limit) were determined before and after NAT and correlated to clinicopathological factors and prognosis. RESULTS The nonhypercoagulation group achieved superior overall survival (OS) than the hypercoagulation group (5-year OS rates = 89% vs. 55%; hazard ratio 3.62, P = 0.0008) when determined according to coagulation status after NAT. Multivariate analysis showed that hypercoagulation after NAT served as an independent factor for poor postoperative OS (hazard ratio 3.20; P = 0.0028). The nonhypercoagulation group achieved significantly better disease-free survival (76% vs. 54%; P = 0.0065) than the hypercoagulation group that experienced a significantly higher rate of hematogenous metastasis as an initial recurrence (P = 0.0337). CONCLUSIONS Hypercoagulation state after NAT served as a valid indicator correlating with postoperative outcomes of patients with ESCC who underwent NAT followed by radical subtotal esophagectomy.
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Affiliation(s)
- Fumitake Sugiyama
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Dai Shimizu
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinichi Umeda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshikuni Inokawa
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Norifumi Hattori
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masamichi Hayashi
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Chie Tanaka
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Goro Nakayama
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Jiang F, Huang X, Ling L, Tang S, Zhou H, Cai X, Wang Y. Long Noncoding RNA ZBED5-AS1 Facilitates Tumor Progression and Metastasis in Lung Adenocarcinoma via ZNF146/ATR/Chk1 Axis. Int J Mol Sci 2023; 24:13925. [PMID: 37762228 PMCID: PMC10530271 DOI: 10.3390/ijms241813925] [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: 06/06/2023] [Revised: 09/06/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis, including lung adenocarcinoma (LUAD). However, the functional and regulatory mechanisms of lncRNAs in LUAD remain poorly understood. In this study, we investigated the role of lncRNA ZBED5-AS1 in LUAD. We found that ZBED5-AS1 was upregulated in LUAD specimens and overexpressed in LUAD cell lines. ZBED5-AS1 promoted LUAD cell proliferation, migration, and invasion in vitro and promoted LUAD cell growth in vivo. ZBED5-AS1 promoted ZNF146 expression, activating the ATR/Chk1 pathway and leading to LUAD progression. We observed that exosomes from LUAD cells have a higher expression of ZBED5-AS1 compared with exosomes from the normal cell line BEAS-2B. Coculture experiments with exosomes showed that ZBED5-AS1 expression was downregulated after coculture with Si-ZBED5-AS1 exosomes, and coculture with exosomes with low ZBED5-AS1 expression inhibited proliferation and invasion of LUAD cells. Our results indicate that ZBED5-AS1 functions as an oncogenic factor in LUAD cells by targeting the ZNF146/ATR/Chk1 axis.
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Affiliation(s)
- Feng Jiang
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; (F.J.)
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou 325015, China
| | - Xiaolu Huang
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; (F.J.)
| | - Liqun Ling
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; (F.J.)
| | - Shiyi Tang
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; (F.J.)
| | - Huixin Zhou
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; (F.J.)
| | - Xueding Cai
- Department of Respiration, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
| | - Yumin Wang
- Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; (F.J.)
- Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou 325015, China
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6
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Magné N, Daguenet E, Bouleftour W, Conraux L, Tinquaut F, Grangeon K, Moreno-Acosta P, Suchaud JP, Rancoule C, Guy JB. Impact of Radiation Therapy on Biological Parameters in Cancer Patients: Sub-analysis from the RIT Prospective Epidemiological Study. Cancer Invest 2023; 41:109-118. [PMID: 36278830 DOI: 10.1080/07357907.2022.2139838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Scarce data investigate the impact of radiotherapy (RT) on biology markers. An analysis of ancillary study of RIT (Radiation Impact on Thromboembolic events) prospective trial was carried out. All patients with non-metastatic solid tumors and treated with radiotherapy and/or brachytherapy in curative and consenting to have blood samples were included. A significant decrease in white blood count, (i.e. lymphocytes, monocytes, neutrophils and basophils) and platelet counts was observed after RT and maintained at 6 months. Whereas, eosinophils, D-dimers and hemoglobin levels were affected respectively 3 months and 6 months after RT initiation. Conversely, red cells count and CRP level were not affected by RT. This study is an advocacy to develop an understanding of basic immune system in relation with RT.
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Affiliation(s)
- Nicolas Magné
- Department of Radiation Oncology, Saint Priest en Jarez, France.,Department of Research and Teaching in Oncology, Saint Priest en Jarez, France.,Molecular and cellular radiobiology Lab, CNRS UMR 5822, Institut de Physique Nucléaire de Lyon, IPNL, Lyon Medicine University, Lyon, France
| | - Elisabeth Daguenet
- Department of Research and Teaching in Oncology, Saint Priest en Jarez, France
| | - Wafa Bouleftour
- Department of Research and Teaching in Oncology, Saint Priest en Jarez, France
| | - Laurine Conraux
- Department of Radiation Oncology, Saint Priest en Jarez, France.,Department of Research and Teaching in Oncology, Saint Priest en Jarez, France
| | - Fabien Tinquaut
- Department of Research and Teaching in Oncology, Saint Priest en Jarez, France
| | - Kevin Grangeon
- Department of Research and Teaching in Oncology, Saint Priest en Jarez, France
| | - Pablo Moreno-Acosta
- Research Group in Radiobiology Clinical, Molecular and Cellular, National Cancer Institute, Bogota, Colombia
| | | | - Chloé Rancoule
- Department of Radiation Oncology, Saint Priest en Jarez, France.,Department of Research and Teaching in Oncology, Saint Priest en Jarez, France
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7
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Qiao W, Sha S, Song J, Chen Y, Lian G, Wang J, Zhou X, Peng L, Li L, Tian F, Jing C. Association between multiple coagulation-related factors and lymph node metastasis in patients with gastric cancer: A retrospective cohort study. Front Oncol 2023; 13:1099857. [PMID: 36910598 PMCID: PMC9996287 DOI: 10.3389/fonc.2023.1099857] [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: 11/16/2022] [Accepted: 01/30/2023] [Indexed: 02/25/2023] Open
Abstract
Background Patients with tumors generally present with accompanying activation of the coagulation system, which may be related to tumor stage. To our knowledge, few studies have examined the activation of the coagulation system in reference to lymph node metastasis within gastric cancer. This study aimed to investigate the correlation between multiple coagulation-related factors and lymph node metastasis in patients with gastric cancer after excluding the influence of tumor T stage. Materials and methods We retrospectively evaluated the relationship between lymph node metastasis and coagulation-related factors in 516 patients with T4a stage gastric cancer. We further analyzed influencing factors for lymph node metastasis and verified the predictive value of maximum amplitude (MA, a parameter of thromboelastography which is widely used to assess the strength of platelet-fibrinogen interaction in forming clots) in reference to lymph node metastasis. Results Platelet counts (P=0.011), fibrinogen levels (P=0.002) and MA values (P=0.006) were statistically significantly higher in patients with T4a stage gastric cancer presenting with lymph node metastasis than in those without lymph node metastasis. Moreover, tumor N stage was statistically significantly and positively correlated with platelet count (P<0.001), fibrinogen level (P=0.003), MA value (P<0.001), and D-dimer level (P=0.010). The MA value was an independent factor for lymph node metastasis (β=0.098, 95% CI: 1.020-1.193, P=0.014) and tumor N stage (β=0.059, 95% CI: 0.015-0.104, P=0.009), and could be used to predict the presence of lymph node metastasis in patients with gastric cancer (sensitivity 0.477, specificity 0.783, P=0.006). The independent influencing factors for MA value mainly included platelet levels, fibrinogen levels, D-dimer and hemoglobin levels; we found no statistically significant correlations with tumor diameter, tumor area, and other evaluated factors. Conclusion We conclude that MA value is an independent influencing factor for lymph node metastasis and tumor N stage in patients with T4a stage gastric cancer. The MA value has important value in predicting the presence or absence of lymph node metastasis in patients with gastric cancer. Clinical trial registration http://www.chictr.org.cn, identifier ChiCTR2200064936.
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Affiliation(s)
- Wenhao Qiao
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Shengxu Sha
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Jiyuan Song
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Yuezhi Chen
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.,Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Guodong Lian
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.,Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Junke Wang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xinxiu Zhou
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Lipan Peng
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.,Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.,Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Feng Tian
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.,Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Changqing Jing
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.,Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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8
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Sano J, Matsuda S, Kawakubo H, Takemura R, Okui J, Irino T, Fukuda K, Nakamura R, Kitagawa Y. ASO Author Reflections: Can We Target a Postoperative Hypercoagulable State in the Acute Phase after Esophagectomy for Esophageal Cancer? Ann Surg Oncol 2022; 29:10.1245/s10434-022-11660-8. [PMID: 35359170 DOI: 10.1245/s10434-022-11660-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 11/18/2022]
Affiliation(s)
- Junichi Sano
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Satoru Matsuda
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
| | - Ryo Takemura
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Jun Okui
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan
| | - Tomoyuki Irino
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Kazumasa Fukuda
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Rieko Nakamura
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
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9
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Sano J, Matsuda S, Kawakubo H, Takemura R, Okui J, Irino T, Fukuda K, Nakamura R, Kitagawa Y. Exposure to a Postoperative Hypercoagulable State Predicts Poor Prognosis After Transthoracic Esophagectomy in Patients with Esophageal Cancer. Ann Surg Oncol 2022; 29:10.1245/s10434-022-11591-4. [PMID: 35347519 DOI: 10.1245/s10434-022-11591-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 02/21/2022] [Indexed: 02/21/2024]
Abstract
PURPOSE The contribution of postoperative coagulation-fibrinolysis status to prognosis is yet to be fully investigated. Thus, in this study, we aimed to elucidate the relationship between postoperative hypercoagulable state (PHS) after transthoracic esophagectomy and long-term outcome in patients with esophageal cancer. METHODS Patients with esophageal cancer who underwent transthoracic esophagectomy were selected from a prospectively maintained database. Based on the trend of postoperative plasma fibrin-fibrinogen degradation product (FDP) levels, patients with PHS were identified. The prognostic significance of PHS was evaluated via multivariate analysis using the Cox regression model. RESULTS Based on the plasma FDP levels of 172 patients that reached a plateau between POD5 and POD7, we calculated the mean FDP value of POD5, 6, and 7, setting a median value as a cutoff. Consequently, 87 patients were classified as PHS. The overall survival (OS) in the PHS group was determined to be significantly lower than in the non-PHS group (5-year OS; 68% and 80%, p = 0.012). Recurrence-free survival (RFS) in the PHS group was significantly lower than in the non-PHS group (5-year RFS; 60% and 79%, p = 0.017). Using the pathological stage as a covariate in the multivariate analysis, PHS was an independent prognostic factor of OS [hazard ratio (HR) 2.517, p = 0.009] and RFS (HR 1.905, p = 0.041). CONCLUSIONS PHS was found to be an independent negative prognostic factor in patients with esophageal cancer. Possible improvement of the oncological outcome by early postoperative intervention with anticoagulants should be explored in clinical trials.
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Affiliation(s)
- Junichi Sano
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Satoru Matsuda
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
| | - Ryo Takemura
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Jun Okui
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
- Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan
| | - Tomoyuki Irino
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Kazumasa Fukuda
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Rieko Nakamura
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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10
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Deme D, Kovacs S, Telekes A. Overall Survival Prediction of Advanced Cancer Patients by Selection of the Most Significant Baseline Serum Biomarker Combination. PATHOLOGY AND ONCOLOGY RESEARCH 2022; 28:1610004. [PMID: 35173556 PMCID: PMC8842665 DOI: 10.3389/pore.2022.1610004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/04/2022] [Indexed: 12/23/2022]
Abstract
Introduction: Consistent association between elevated baseline serum values and C-reactive protein (CRP), cross-linked fibrin degradation products (D-dimer), lactate dehydrogenase (LDH), decreased baseline serum albumin, absolute lymphocyte count to absolute monocyte count ratio (LMR), elevated absolute neutrophil count to absolute lymphocyte count ratio (NLR), elevated platelet count to absolute lymphocyte count ratio (PLR), and between some combinations of these biomarkers and the short overall survival of patients with malignant diseases has already been reported. These biomarkers are independent prognostic factors for cancer. Here, the most significant biomarker combination of these values was searched and studied in real-life advanced cancer patients of a single center.Methods: The authors retrospectively analyzed the association of the aforementioned biomarkers and their combination and OS of 75 consecutive cancer patients with locally advanced, recurrent, or metastatic diseases. Validated cut-off determination was used.Results: CRP, albumin, and PLR showed marked association with OS. Cut-off values for significant shorter OS were 30.65 mg/L (p < 0.001), 44.35 g/L (p < 0.001), and 168.20 (p < 0.001), respectively. Based on assessed biomarker cut-offs, four patient groups were created to determine whether biomarker values were out of range (ORV) compared to cut-off: 1) No ORV biomarkers (n = 24; OS = 26.07 months); 2) one ORV biomarker (n = 21; OS = 13.50 months); 3) two ORV biomarkers (n = 20; OS = 7.97 months), and 4) three ORV biomarkers (n = 10; OS = 3.91 months). Significant differences in OS were detected between the groups: For 1. vs. 2. hazard ratio (HR) = 3.0 (95% CI: 1.5–6.2), p = 0.003; for 1. vs. 3. HR = 4.1 (95% CI: 2.0–8.3), p < 0.001; and for 1. vs. 4. HR = 10.2 (95% CI: 4.2–24.6), p < 0.001.Conclusion: Based on our analysis, we can confirm that the complex monitoring of CRP, albumin, and PLR would provide a good estimation of OS. Large scale prospective studies are warranted to explore this and other useful combinations of prognostic biomarkers and their relationship to the well-established prognostic systems in real-life.
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Affiliation(s)
- Daniel Deme
- Department of Medical Oncology, Szent Lázár County Hospital, Salgótarján, Hungary
- *Correspondence: Daniel Deme,
| | - Sandor Kovacs
- Department of Economical and Financial Mathematics, University of Debrecen, Debrecen, Hungary
| | - Andras Telekes
- Department of Medical Oncology, Szent Lázár County Hospital, Salgótarján, Hungary
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11
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Yan Q, Ni C, Lin Y, Sun X, Shen Z, Zhang M, Han S, Shi J, Mao J, Yang Z, Wang W. ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis. Front Mol Biosci 2021; 8:764900. [PMID: 34966781 PMCID: PMC8711721 DOI: 10.3389/fmolb.2021.764900] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 11/22/2021] [Indexed: 12/24/2022] Open
Abstract
Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer in vitro and in vivo. Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer via LGMN and conferred poor prognosis.
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Affiliation(s)
- Qiang Yan
- Department of General Surgery, Huzhou Central Hospital, Huzhou, China
| | - Chenming Ni
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Shanghai, China
| | - Yingying Lin
- Department of Neurosurgery, RenJi Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Xu Sun
- Department of General Surgery, Huzhou Central Hospital, Huzhou, China
| | - Zhenhua Shen
- Department of General Surgery, Huzhou Central Hospital, Huzhou, China
| | - Minjie Zhang
- Department of General Surgery, Huzhou Central Hospital, Huzhou, China
| | - Shuwen Han
- Department of General Surgery, Huzhou Central Hospital, Huzhou, China
| | - Jiemin Shi
- Department of General Surgery, Huzhou Central Hospital, Huzhou, China
| | - Jing Mao
- Department of General Surgery, Huzhou Central Hospital, Huzhou, China
| | - Zhe Yang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China
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12
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Liu F, Hu HJ, Regmi P, Jin YW, Ma WJ, Wang JK, Zou RQ, Li FY. Elevated Platelet Distribution Width Predicts Poor Prognosis in Gallbladder Carcinoma. Cancer Manag Res 2021; 13:4647-4655. [PMID: 34140810 PMCID: PMC8203277 DOI: 10.2147/cmar.s311061] [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: 03/14/2021] [Accepted: 05/27/2021] [Indexed: 02/05/2023] Open
Abstract
Background Previous studies have demonstrated that platelet distribution width (PDW) is a reliable predictor of prognosis of a variety of tumors. Nevertheless, the prognostic value of PDW in gallbladder carcinoma (GBC) remains unknown. We aimed to explore the correlation between PDW and prognosis in patients with GBC. Methods A total of 303 patients with GBC who underwent curative surgery between January 2005 and February 2017 were enrolled. The relationship between PDW and clinicopathological features was analyzed. Receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value of PDW. The overall survival (OS) rate was estimated by Kaplan–Meier method. Meanwhile, univariable and multivariable Cox regression model were used to evaluate the risk factors for OS. Results There was significant correlation between elevated PDW and AJCC stage. In addition, survival analysis revealed that the patients with PDW>14.95 have a worse prognosis than patients with PDW\documentclass[12pt]{minimal}
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\end{document}14.95 (P < 0.001). The multivariable Cox regression model analysis demonstrated that PDW was an independent prognostic factor in GBC patients (hazard ratio=1.976, 95% confidence interval:1.474–2.650, P<0.001). Conclusion Elevated PDW can predict poor prognosis in GBC patients, and further studies are needed to verify the reliability and clarify the exact molecular mechanistic of PDW in GBC.
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Affiliation(s)
- Fei Liu
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Parbatraj Regmi
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Yan-Wen Jin
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Jun-Ke Wang
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Rui-Qi Zou
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China
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13
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Preoperative plasma D-dimer independently predicts survival in patients with pancreatic ductal adenocarcinoma undergoing radical resection. World J Surg Oncol 2021; 19:166. [PMID: 34107980 PMCID: PMC8191214 DOI: 10.1186/s12957-021-02281-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/31/2021] [Indexed: 12/16/2022] Open
Abstract
Background Elevated plasma D-dimer levels have been reported as an unfavorable prognostic indicator in many solid tumors. However, there are limited relevant studies in pancreatic cancer patients following radical surgery, and the clinical significance remains controversial. The aim of this study was to investigate the clinical and prognostic significance of preoperative plasma D-dimer in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection. Methods A retrospective analysis was performed on all patients who consecutively underwent radical surgery for PDAC by laparotomy or robotic surgery from December 2011 to December 2018. Baseline clinicopathologic characteristics, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to analyze the prognostic value of preoperative plasma D-dimer. Results Among 1351 patients, elevated preoperative plasma D-dimer levels (≥ 0.55 ng/mL) were found in 417 (30.9%) patients. Three hundred twelve (23.09%) underwent minimally invasive robotic pancreatectomy. The median overall survival (OS) of patients with elevated D-dimer levels was 6.3 months shorter than that of patients with normal D-dimer levels (15.0 months vs 21.3 months, p < 0.001). Multivariate analysis showed that elevated D-dimer levels independently predicted poorer OS (hazard ratio, 1.33; 95% confidence interval, 1.17-1.51, p < 0.001). Subgroup analysis demonstrated that D-dimer was a reliable prognostic factor in patients who underwent R0 resection. In addition, integration of D-dimer, carbohydrate antigen 19-9 (CA19-9), and NLR provided a better prognostic model for PDAC patients before operation. Conclusion An elevated preoperative plasma D-dimer level was a reliable independent prognostic factor for OS in patients with PDAC undergoing resection. Combination of D-dimer, CA19-9, and NLR can enhance the prognostic accuracy before operation. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02281-8.
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14
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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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15
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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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Fang L, Xu Q, Qian J, Zhou JY. Aberrant Factors of Fibrinolysis and Coagulation in Pancreatic Cancer. Onco Targets Ther 2021; 14:53-65. [PMID: 33442266 PMCID: PMC7797325 DOI: 10.2147/ott.s281251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/11/2020] [Indexed: 12/13/2022] Open
Abstract
Aberrant factors associated with fibrinolysis and thrombosis are found in many cancer patients, which can promote metastasis and are associated with poor prognosis. The relationship between tumor-associated fibrinolysis and thrombosis is poorly understood in pancreatic cancer. This review provides a brief highlight of existing studies that the fibrinolysis and coagulation systems were activated in pancreatic cancer patients, along with aberrant high concentrations of tissue plasminogen activator (t-PA), urine plasminogen activator (u-PA), D-dimer, fibrinogen, or platelets. These factors cooperate with each other, propelling tumor cell shedding, localization, adhesion to distant metastasis. The relationship between thrombosis or fibrinolysis and cancer immune escape is also investigated. In addition, the potential prevention and therapy strategies of pancreatic cancer targeting factors in fibrinolysis and coagulation systems are also been discussed, in which we highlight two effective agents aspirin and low-molecular weight heparin (LMWH). Summarily, this review provides new directions for the research and treatment of pancreatic cancer.
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Affiliation(s)
- Lianghua Fang
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, People's Republic of China
| | - Qing Xu
- Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210029, People's Republic of China
| | - Jun Qian
- Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, People's Republic of China
| | - Jin-Yong Zhou
- Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, People's Republic of China
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Abnormal pretreatment coagulation factor levels correlate with poor prognosis in patients with early-stage extranodal nasal-type natural/killer T cell lymphoma. Ann Hematol 2020; 99:1303-1309. [PMID: 32333152 DOI: 10.1007/s00277-020-04035-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Accepted: 04/10/2020] [Indexed: 12/28/2022]
Abstract
Coagulative dysfunction is frequently observed among patients with extranodal nasal-type natural killer/T cell lymphoma (NKTCL) in our clinical practice. However, the true prognostic value of coagulation factors in patients with NKTCL has not been evaluated systemically. Data for patients with stage I/II NKTCL who were treated in the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2008 to January 2019 were collected retrospectively. The patients enrolled in this study were initially diagnosed as having early-stage disease. The patients' baseline characteristics and pretreatment laboratory tests for coagulation function, including fibrinogen (FIB) and D-dimer (D-D), were reviewed and analyzed. The influence of coagulative factors on the responses and prognosis of patients with early-stage NKTCL was evaluated. Among 394 patients assessed, 154 were included in this study. Abnormal coagulation function was found in nearly half of the patients (48.1%). Univariate analysis showed that reduced complete remission (CR) was associated with elevated D-D (P = 0.001) and elevated FIB levels (P = 0.006). The D-D level was demonstrated as associated with unfavorable progression-free survival (PFS) (P = 0.003) and overall survival (OS) (P = 0.002). Multivariate analysis indicated that an elevated D-D level was an independent factor for poor clinical response (P = 0.019), PFS (P = 0.046), and OS (P = 0.024). Elevated pretreatment levels of coagulation factors, especially D-D and plasma FIB, are unfavorable predictors for clinical response, OS, and PFS in early-stage NKTCL.
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Hara K, Aoyama T, Hayashi T, Nakazono M, Nagasawa S, Shimoda Y, Kumazu Y, Numata M, Yamada T, Tamagawa H, Shiozawa M, Morinaga S, Yukawa N, Rino Y, Masuda M, Ogata T, Oshima T. Postoperative D-dimer elevation affects tumor recurrence and the long-term survival in gastric cancer patients who undergo gastrectomy. Int J Clin Oncol 2019; 25:584-594. [PMID: 31865480 DOI: 10.1007/s10147-019-01603-x] [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: 07/12/2019] [Accepted: 12/11/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION We retrospectively evaluated the blood coagulation activity using the D-dimer level in the early period after gastrectomy and investigated whether postoperative hypercoagulation affects tumor recurrence and long-term survival in gastric cancer patients. METHODS The study involved 650 patients who underwent curative resection for gastric cancer at Kanagawa Cancer Center between July 2009 and July 2013. They were divided into a low-D-dimer group (LD group) and high-D-dimer group (HD group) according to the median D-dimer level on postoperative day (POD) 7. The risk factors for overall survival (OS) and relapse-free survival (RFS) were identified. RESULTS Of the 448 enrolled patients, 218 were classified into the LD group and 230 into the HD group. The 5-year OS rates after surgery were 90.8% and 81.3% in the LD and HD groups, respectively (p < 0.001). The 5-year RFS rates after surgery were 89.9% and 76.1% in the LD and HD groups, respectively (p < 0.001). A high D-dimer level on POD 7 (≥ 4.9 μg/ml) was identified as an independent predictive factor for both the OS (hazard ratio [HR] 1.955, 95% confidence interval [CI] 1.158-3.303, p = 0.012) and RFS (HR 2.182, 95% CI 1.327-3.589, p = 0.002). Furthermore, hematological recurrence was significantly more frequent in the HD group than in the LD group (p = 0.014). CONCLUSION A high D-dimer level on POD 7 may predict tumor recurrence and the long-term survival in patients who undergo gastrectomy for locally advanced gastric cancer. Patients with an elevated postoperative D-dimer level need careful observation and diagnostic imaging to timely detect tumor recurrence.
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Affiliation(s)
- Kentaro Hara
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Tsutomu Hayashi
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Masato Nakazono
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Shinsuke Nagasawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Yota Shimoda
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Yuta Kumazu
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Masakatsu Numata
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Takanobu Yamada
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Hiroshi Tamagawa
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Manabu Shiozawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Soichiro Morinaga
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Norio Yukawa
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Takashi Ogata
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan
| | - Takashi Oshima
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
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Song Q, Wu JZ, Wang S, Chen WH. Elevated preoperative platelet distribution width predicts poor prognosis in Esophageal Squamous Cell Carcinoma. Sci Rep 2019; 9:15234. [PMID: 31645619 PMCID: PMC6811575 DOI: 10.1038/s41598-019-51675-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 10/07/2019] [Indexed: 01/10/2023] Open
Abstract
Activated platelets play a multifaceted role in tumorigenesis and progression. Platelet distribution width (PDW) is generally applied platelet parameters from routine blood test. Preoperative PDW has been considered a prognostic factor in many cancers. Nevertheless, the prognostic value of PDW in esophageal squamous cell carcinoma (ESCC) remains unknown. The study aimed to investigate whether preoperative PDW could serve as a prognostic factor in patients with ESCC. A total of 495 patients with ESCC undergoing curative surgery were enrolled. The relationship between PDW and clinical features in ESCC was analyzed using chi-square tests. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value. Overall survival (OS) and disease-free survival (DFS) stratified by PDW were evaluated by Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression were used to evaluate the prognostic effect of PDW. Of the 495 patients, elevated PDW was observed in 241(48.7%) of the patients, respectively. An elevated PDW was correlated with depth of tumor (T stage, P = 0.031), nerve infiltration (P = 0.016), hospital time after operation (P = 0.020), platelet (P < 0.001), red cell distribution width (P < 0.001), and aspartate transaminase (P = 0.001). Moreover, elevated PDW (PDW ≥ 13.4 fL) predicted a worse OS and DFS in patients with ESCC (both P < 0.001). Multivariate analyses revealed that PDW was independently associated with OS (hazard ratios 1.194; 95% confidence interval 1.120-1.273; P < 0.001) and DFS (hazard ratios 2.562; 95% confidence interval 1.733-3.786; P < 0.001). Our findings indicated that elevated PDW could serve as an independent worse survival in ESCC.
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Affiliation(s)
- Qian Song
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences; Department of Clinical Laboratory, Cancer Hospital of the University of Chinese Academy of Sciences; Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People's Republic of China
| | - Jun-Zhou Wu
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences; Cancer Research Institute, Cancer Hospital of the University of Chinese Academy of Sciences; Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People's Republic of China
| | - Sheng Wang
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences; Department of Clinical Laboratory, Cancer Hospital of the University of Chinese Academy of Sciences; Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People's Republic of China
| | - Wen-Hu Chen
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences; Department of Clinical Laboratory, Cancer Hospital of the University of Chinese Academy of Sciences; Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People's Republic of China.
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Differential Expression and Diagnostic Significance of Pre-Albumin, Fibrinogen Combined with D-Dimer in AFP-Negative Hepatocellular Carcinoma. Pathol Oncol Res 2019; 26:1669-1676. [PMID: 31578661 DOI: 10.1007/s12253-019-00752-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 09/12/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most malignant cancers with high morbidity and mortality. Nowadays, AFP-negative hepatocellular carcinoma (AFP-NHCC) has been found in many HCC patients and AFP analysis can't be used to screen HCC in these cases. In this study, we have examined the expression patterns of pre-albumin (PA), fibrinogen, D-Dimer and their clinical significance in AFP-NHCC. We recruited 214 AFP-NHCC patients and 210 controls in the study. PA, fibrinogen and D-Dimer levels were detected by turbidimetry, clauss and immunoturbidimetry methods, respectively. Serum PA levels were significantly lower in AFP-NHCC (84.5 ± 24.7 mg/L) than that in the controls (240.6 ± 59.4 mg/L, P < 0.05). For plasma fibrinogen levels, there was no difference between the controls (2.9 ± 0.7 g/L) and AFP-NHCC (2.5 ± 0.7 g/L). Compared with AFP-NHCC (0.8 ± 0.2 mg/L), plasma D-Dimer levels were significantly lower in controls (0.1 ± 0.0 mg/L, P < 0.05). The levels of PA, fibrinogen and D-Dimer were significantly correlated with differentiation (P < 0.01), and the PA and D-Dimer values were correlated with TNM stage (P < 0.05). Moreover, PA levels were correlated with tumor size (P = 0.034). Receiver operating characteristic curve (ROC) analyses elaborated that combination of PA, fibrinogen and D-Dimer possessed a higher sensitivity (93.4%) for differentiating AFP-NHCC from the controls, but the diagnostic specificity was reduced due to the combination of fibrinogen. After adjusting for all significant outcome predictors of the univariate logistic regression analysis, low levels of PA and high levels of D-Dimer were remained independent unfavorable outcome predictors (P < 0.05). Our data suggested that the expression levels of PA, fibrinogen and D-Dimer played critical roles in AFP-NHCC tumorigenesis. Moreover, PA and D-Dimer might be considered as potential diagnostic indicators in AFP-NHCC.
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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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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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Zhu X, Cao Y, Lu P, Kang Y, Lin Z, Hao T, Song Y. Evaluation of platelet indices as diagnostic biomarkers for colorectal cancer. Sci Rep 2018; 8:11814. [PMID: 30087357 PMCID: PMC6081379 DOI: 10.1038/s41598-018-29293-x] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 07/09/2018] [Indexed: 02/08/2023] Open
Abstract
Altered platelet indices, including platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT), have been found in various cancer types. This study aimed to evaluate the role of platelet indices as potential biomarkers for the diagnosis of colorectal cancer (CRC), and to assess the association between platelet indices and CRC clinicopathological characteristics. The study included 783 subjects with CRC, 463 subjects with colorectal adenomas (CA), and 689 control subjects from June 2015 to October 2017. All participants' clinicopathological characteristics were collected and analyzed. Here, we found that PC, MPV and PCT levels in CRC patients were significantly higher than those in CA patients and healthy participants (p < 0.001); however, PDW level in CRC patients was significantly higher than that in healthy participants while lower than that in CA patients. Receiver-operating characteristic (ROC) analysis indicated that combined detection of PCT and CEA appears to be a more effective marker to distinguish CRC patients from CA patients, with 70% sensitivity and 83% specificity. Among CRC patients, PC and PCT levels were associated with TNM stages and tumor size; MPV and PCT levels were associated with vascular invasion. Our findings suggest that altered PC, MPV and PCT levels might serve as potential biomarkers for the diagnosis and prognosis of CRC.
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Affiliation(s)
- Xianjin Zhu
- Department of Laboratory Medicine, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, China
| | - Yingping Cao
- Department of Laboratory Medicine, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, China
| | - Pingxia Lu
- Department of Laboratory Medicine, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, China
| | - Yanli Kang
- Department of Laboratory Medicine, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, China
| | - Zhen Lin
- Department of Laboratory Medicine, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, China
| | - Taisen Hao
- Department of Cancer Biology, Beckman Research Institute, City of Hope, Duarte, California, 91010, USA
| | - Yanfang Song
- Department of Laboratory Medicine, Clinical Laboratory, Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, 602 Bayiqi Road, Fuzhou, 350001, China.
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Yan Q, Yuan WB, Sun X, Zhang MJ, Cen F, Zhou SY, Wu WB, Xu YC, Tong LH, Ma ZH. Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis. Int J Oncol 2018; 52:1651-1660. [PMID: 29568945 DOI: 10.3892/ijo.2018.4318] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 03/07/2018] [Indexed: 11/06/2022] Open
Abstract
Pancreatic cancer is one of the most lethal types of cancer; owing to low early detection rates and high metastasis rates, it is associated with an extremely poor prognosis. Therefore, a better understanding of the molecular mechanisms that underlie its metastasis and the identification of potential prognostic biomarkers are urgently required. Although high expression levels of asparaginyl endopeptidase (AEP) have been detected in various types of solid tumor, the expression and functions of AEP in pancreatic carcinomas have yet to be determined. The present study aimed to examine the putative functions of AEP in pancreatic carcinoma. Immunohistochemical analysis revealed that AEP was highly expressed in pancreatic cancer tissues compared with adjacent normal tissues. Patients with high AEP expression exhibited a significantly shorter overall survival time. Results from multivariate Cox regression analysis revealed that AEP was an independent prognostic factor for overall survival. Gain- and loss-of-function experiments demonstrated that knockdown of AEP expression significantly reduced the invasive ability of pancreatic cancer cells, whereas overexpression of AEP increased the invasive ability. In addition, AEP was detected in exosomes that were derived from cultured pancreatic ductal adenocarcinoma cells (PDACs) and in the serum from patients with PDAC. The Matrigel-Transwell invasion assay revealed that exosomes enriched with AEP were able to enhance the invasive ability of PDAC cells, whereas exosomes lacking AEP decreased the invasive ability. Furthermore, results from the present study suggested that AEP may be crucial for activation of the phosphoinositide 3-kinase/RAC‑α serine/threonine-protein kinase signaling pathway in PDAC cells. The present study data indicated that high AEP expression may be important for pancreatic carcinoma progression in an exosome-dependent manner, and that AEP may be an independent indicator of poor prognosis in patients with PDAC and may be a novel prognostic biomarker or therapeutic target in pancreatic carcinoma.
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Affiliation(s)
- Qiang Yan
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Wen-Bin Yuan
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Xu Sun
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Ming-Jie Zhang
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Feng Cen
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Shi-Yu Zhou
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Wan-Bo Wu
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Yong-Can Xu
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Li-Hui Tong
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
| | - Zhi-Hong Ma
- Department of General Surgery, Huzhou Central Hospital, Huzhou, Zhejiang 313003, P.R. China
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Deng J, Zhang P, Sun Y, Peng P, Huang Y. Prognostic and clinicopathological significance of platelet to lymphocyte ratio in esophageal cancer: a meta-analysis. J Thorac Dis 2018; 10:1522-1531. [PMID: 29707302 DOI: 10.21037/jtd.2018.02.58] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background The prognostic and clinicopathological significance of the platelet to lymphocyte ratio (PLR) has been studied in various cancers. However, studies examining the role of PLR in esophageal cancer have not yielded consistent results. The purpose of this meta-analysis was to study the prognostic and clinicopathological significance of PLR in esophageal cancer patients. Methods We performed a literature search in three major databases: PubMed, Web of Science and Embase (up until May 1, 2017). The clinicopathologic significance of PLR and its prognostic significance were analyzed. Results Our meta-analysis consisted of 13 studies with 4,621 patients. The pooled hazard ratios (HRs) showed that a high PLR was associated with poor survival of esophageal cancer [HR =1.283; 95% confidence interval (CI): 1.173-1.404; P<0.001]. Subgroup analysis revealed that elevated PLR was associated with poor survival in esophageal squamous cell carcinoma (HR =1.281; 95% CI: 1.098-1.493; P=0.002). The pooled odds ratio (OR) indicated that high PLR was also associated with the depth of tumor invasion (OR =1.543, 95% CI: 1.269-1.876, P<0.001), lymph node metastasis (OR =1.427, 95% CI: 1.195-1.705, P<0.001), tumor length (OR =1.81, 95% CI: 1.331-2.461, P<0.001), and Tumor stage (OR =1.459, 95% CI: 1.235-1.724, P<0.001). Conclusions Our results demonstrate that elevated PLR was significantly associated with poor prognosis of esophageal cancer. Furthermore, the high PLR might predict worse clinicopathological features of esophageal cancer patients.
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Affiliation(s)
- Juhong Deng
- Department of Endocrinology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Peng Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yue Sun
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Ping Peng
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Yu Huang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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Chen S, Na N, Jian Z. Pretreatment platelet count as a prognostic factor in patients with pancreatic cancer: a systematic review and meta-analysis. Onco Targets Ther 2017; 11:59-65. [PMID: 29317834 PMCID: PMC5743191 DOI: 10.2147/ott.s147715] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background The relationship between platelet counts and pancreatic cancer as a prognostic factor has been reported in many studies. We aimed to evaluate the prognostic value of platelet counts in predicting the prognosis of pancreatic cancer patients. Methods We searched PubMed, Medline, EMBASE, and Google Scholar for eligible studies up to May 2017. Information about the characteristics of the study and relevant outcomes was extracted. A meta-analysis was performed to analyze the prognostic value of platelet counts using the hazard ratio (HR) and 95% confidence intervals (CIs). Results A total of 1,756 patients in 13 retrospective studies were included. The pooled HR of 1.51 (95% CI: 1.20–1.90, P<0.001) showed that patients with elevated platelet counts were expected to have poor overall survival after treatment. Subgroup analysis showed that prognostic value of platelet levels was stronger in patients who received surgical resection (HR =1.60, 95% CI: 1.09–2.34, P=0.02), followed by patients who received palliative therapy (HR =1.46, 95% CI: 1.03–2.06, P=0.03). Conclusion Platelet counts could be a useful prognostic marker for pancreatic cancer. Patients with high platelet counts are expected to have poor survival.
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Affiliation(s)
- Sheng Chen
- Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences
| | - Ning Na
- Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Zhixiang Jian
- Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences
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Durczynski A, Skulimowski A, Hogendorf P, Szymanski D, Kumor A, Marski K, Juliebø SØ, Poznanska G, Strzelczyk J. The concentration of D-dimers in portal blood positively correlates with overall survival in patients with non-resectable pancreatic cancer. World J Surg Oncol 2017; 15:223. [PMID: 29246148 PMCID: PMC5732385 DOI: 10.1186/s12957-017-1291-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 12/05/2017] [Indexed: 12/14/2022] Open
Abstract
Background Several recent studies provide evidence that D-dimer (DD) concentration in peripheral blood correlates negatively with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). Contrarily, there are recent evidence indicating that preoperative plasma fibrinogen, but not D-dimer might represent a prognostic factor in non-metastatic gastrointestinal cancers. Methods In a single-center prospective study, we enrolled 62 patients undergoing surgery for pathologically confirmed PDAC without detectable venous thrombosis. Intraoperatively, the sample of the blood from the portal vein was obtained. DD concentration in these samples was measured. Patients were followed postoperatively until time of death from any cause. Results We found that OS for patients with portal blood DD values above 2700 (ng/mL) (n = 22 from 62 patients) was higher by 158% than that for the patients (n = 42) with DD values ≤ 2700 (416 days versus 161 days, p = 0.05). On the contrary to the studies investigating DD concentration in peripheral blood, we have found that patients with higher DD level in the portal vein had longer mean OS than patients with lower ones. Conclusions Further investigation is necessary both to confirm our results in a larger patient population and to elucidate the mechanism for the correlation between portal blood D-dimer concentrations and survival time. Along with other authors, we conclude that portal circulation is characterized by unique, biological environment that requires further evaluation.
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Affiliation(s)
- Adam Durczynski
- Department of General and Transplant Surgery, Barlicki Teaching Hospital, Medical University of Lodz, Kopcinskiego Street 22, 90-153, Lodz, Poland.
| | - Aleksander Skulimowski
- Department of General and Transplant Surgery, Barlicki Teaching Hospital, Medical University of Lodz, Kopcinskiego Street 22, 90-153, Lodz, Poland
| | - Piotr Hogendorf
- Department of General and Transplant Surgery, Barlicki Teaching Hospital, Medical University of Lodz, Kopcinskiego Street 22, 90-153, Lodz, Poland
| | - Dariusz Szymanski
- Department of General and Transplant Surgery, Barlicki Teaching Hospital, Medical University of Lodz, Kopcinskiego Street 22, 90-153, Lodz, Poland
| | - Anna Kumor
- Department of Pulmonology and Allergy, Barlicki Teaching Hospital, Medical University of Lodz, Lodz, Poland
| | - Konrad Marski
- Department of General and Transplant Surgery, Barlicki Teaching Hospital, Medical University of Lodz, Kopcinskiego Street 22, 90-153, Lodz, Poland
| | - Siri Øvereng Juliebø
- Department of General and Transplant Surgery, Barlicki Teaching Hospital, Medical University of Lodz, Kopcinskiego Street 22, 90-153, Lodz, Poland
| | - Grazyna Poznanska
- Department of Anaesthesiology and Intensive Care, Barlicki Teaching Hospital, Lodz, Poland
| | - Janusz Strzelczyk
- Department of General and Transplant Surgery, Barlicki Teaching Hospital, Medical University of Lodz, Kopcinskiego Street 22, 90-153, Lodz, Poland
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Xie X, Zeng X, Cao S, Hu X, Shi Q, Li D, Zhou S, Gu P, Zhang Z. Elevated pretreatment platelet distribution width and platelet count predict poor prognosis in nasopharyngeal carcinoma. Oncotarget 2017; 8:106089-106097. [PMID: 29285316 PMCID: PMC5739703 DOI: 10.18632/oncotarget.22528] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 10/28/2017] [Indexed: 11/25/2022] Open
Abstract
Background Previous studies have demonstrated that platelets play a multifaceted role in cancer progression and metastasis. However, the value of platelet indices for predicting survival in nasopharyngeal carcinoma (NPC) patients remains unknown. The aim of this study was to evaluate the predictive significance of platelet indices in NPC cases. Materials and Methods A total of 168 patients who were diagnosed with NPC between January 2011 and June 2012 were recruited. The optimal cut-off values for the platelet indices were determined using a receiver operating characteristic curve. The Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of the potential predictors. Results Of the 168 patients, high platelet distribution width (PDW) and platelet count (PLT) levels were observed in 81 (48.21%) and 68 (40.48%) of the patients, respectively. An increased PDW was associated with the depth of invasion (T stage, P = 0.019), lymph node metastasis (N stage, P = 0.026), and clinical stage (P < 0.001). Moreover, the survival analysis showed that the overall survival of the patients with a PDW > 16.3 fL or platelet count > 266 × 109/L was associated with a poorer prognosis (both P < 0.001). In the multivariate Cox regression model, the PDW (P < 0.001), PLT (P = 0.001), T stage (P < 0.001), N stage (P = 0.006), clinical stage (P = 0.005), and Epstein-Barr virus DNA (P = 0.039) were independent prognostic factors for the overall survival. Conclusions The PDW and PLT are easily available via a routine blood test, and our study showed that the PDW and PLT could be prognostic predictors in NPC patients. However, further studies are required to confirm this conclusion.
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Affiliation(s)
- XueCheng Xie
- Department of Oncology, The Affiliated Hospital of XiangNan University, Chenzhou, China
| | - XiaoChun Zeng
- Department of Oncology, The Affiliated Hospital of XiangNan University, Chenzhou, China
| | - SuJuan Cao
- Department of Oncology, The Affiliated Hospital of XiangNan University, Chenzhou, China
| | - XiaoMao Hu
- Department of Oncology, The Affiliated Hospital of XiangNan University, Chenzhou, China
| | - QiaoJing Shi
- Department of Oncology, The Affiliated Hospital of XiangNan University, Chenzhou, China
| | - Dan Li
- Department of Oncology, The Affiliated Hospital of XiangNan University, Chenzhou, China
| | - ShiYuan Zhou
- Department of Nuclear Medicine, The Affiliated Hospital of XiangNan University, Chenzhou, China
| | - Ping Gu
- Department of Child Healthcare, Chenzhou First People's Hospital, Chenzhou, China
| | - ZhongShan Zhang
- Department of Oncology, The Affiliated Hospital of XiangNan University, Chenzhou, China
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Liu Z, Guo H, Gao F, Shan Q, Li J, Xie H, Zhou L, Xu X, Zheng S. Fibrinogen and D-dimer levels elevate in advanced hepatocellular carcinoma: High pretreatment fibrinogen levels predict poor outcomes. Hepatol Res 2017; 47:1108-1117. [PMID: 27914119 DOI: 10.1111/hepr.12848] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2016] [Revised: 11/21/2016] [Accepted: 11/27/2016] [Indexed: 12/22/2022]
Abstract
AIM Plasma fibrinogen and D-dimer have been reported to predict survival in several types of malignancies. The aim of this study is to investigate their predictive value in patients with hepatocellular carcinoma (HCC). METHODS We retrospectively analyzed plasma fibrinogen and D-dimer levels from 252 subjects: control (n = 20), hepatitis (n = 20), cirrhosis (n = 20), and HCC (n = 192) subjects. The clinical involvement and prognostic value of fibrinogen and D-dimer was analyzed in HCC subjects. To confirm the effects of tumor on hypercoagulability and fibrinolysis, fibrinogen and D-dimer levels were measured in nude mice following HCC inoculation. RESULTS Fibrinogen decreased and D-dimer increased in cirrhosis subjects relative to other groups. In HCC subjects, elevated fibrinogen and D-dimer levels were significantly associated with adverse tumor features (increased size, stage, and grade) and systemic inflammation. Patients with HCC with either elevated fibrinogen or D-dimer levels had significantly higher 3-year tumor recurrence rates (65% vs. 41%, P < 0.001 for fibrinogen; 67% vs. 40%, P = 0.011 for D-dimer) and significantly lower 3-year overall survival rates (57% vs. 79%, P < 0.001 for fibrinogen; 56% vs. 80%, P = 0.001 for D-dimer). After multivariate analysis, elevated fibrinogen levels remained an independent predictor of poor prognosis in HCC patients. Finally, elevated levels of fibrinogen and D-dimer were confirmed in nude mice following tumor inoculation. CONCLUSION The fibrinogen and D-dimer levels, elevating after carcinogenesis, may serve as simple but effective predictors of adverse tumor profiles and outcomes in 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 Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Haijun Guo
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Feng Gao
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Qiaonan Shan
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Jie Li
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Haiyang Xie
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Lin Zhou
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China
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Cao J, Fu Z, Gao L, Wang X, Cheng S, Wang X, Ren H. Evaluation of serum D-dimer, fibrinogen, and CA19-9 for postoperative monitoring and survival prediction in resectable pancreatic carcinoma. World J Surg Oncol 2017; 15:48. [PMID: 28219450 PMCID: PMC5319056 DOI: 10.1186/s12957-017-1104-9] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 01/18/2017] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND We sought to investigate the efficacy of serum D-dimer, fibrinogen, and CA19-9 for postoperative monitoring and prediction of survival in patients with resectable pancreatic carcinoma (PC). METHODS One hundred and nineteen patients with resectable PC were enrolled. Serum D-dimer, fibrinogen, and CA19-9 values were analyzed before surgery and at the stages of relapse-free and progression disease. RESULTS D-dimer, fibrinogen, and CA19-9 were significantly higher at the active stage of PC than those at the relapse-free stage [1059.2 (1690.1) ng/ml vs 485.18 (289.84) ng/ml, (3.71 ± 0.83) g/l vs (2.75 ± 0.52) g/l, 207.2 (681.8) U/ml vs 24.5 (30) U/ml, respectively, p < 0.01]. Patients with elevated preoperative D-dimer had significantly shorter overall survival (18.9 ± 1.9 months vs 29.2 ± 2.6 months, p < 0.01) and progression-free survival (10.6 ± 1.2 months vs 20.4 ± 2.4 months, p < 0.01) than did those with low D-dimer. The correlation between CA19-9 values and survival depended on the threshold value of CA19-9: when the threshold value was 37 U/ml, there was no correlation between CA19-9 and survival; when the threshold value was 253.8 U/ml (median CA19-9 for the enrolled patients), patients with elevated preoperative CA19-9 had significantly shorter overall survival (19.9 ± 2. 1 months vs 29.0 ± 2. 7 months) and progression-free survival (11.5 ± 1.5 months vs 21.0 ± 2. 6 months) than did the patients with low CA19-9 (p < 0.01); when the threshold value was 1000 U/ml, the overall survival was 15.5 ± 2.3 months vs 28.0 ± 2.0 months and the progression-free survival 8.9 ± 1.9 months vs 19.1 ± 1.9 months (p < 0.01). There was no correlation between fibrinogen and overall survival (25.8 ± 2.1 months vs 21.2 ± 2.9 months; p = 0.096) and progression-free survival (17.8 ± 2.1 months vs 12.7 ± 1.7 months; p = 0.168). CONCLUSIONS For postoperative monitoring of patients with resectable PC, D-dimer, fibrinogen, and CA19-9 may be used as markers for monitoring disease relapse, but only preoperative D-dimer could predict survival.
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Affiliation(s)
- Junli Cao
- Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 People’s Republic of China
| | - Zhanzhao Fu
- Department of Oncology, First Hospital of Qinhuangdao, Hebei, 066000 People’s Republic of China
| | - Liming Gao
- Department of Oncology, First Hospital of Qinhuangdao, Hebei, 066000 People’s Republic of China
| | - Xin Wang
- Department of Intensive Medicine, Traditional Chinese Medicine Hospital of Qinhuangdao, Hebei, 066000 People’s Republic of China
| | - Shaohui Cheng
- Department of Oncology, First Hospital of Qinhuangdao, Hebei, 066000 People’s Republic of China
| | - Xiuchao Wang
- Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 People’s Republic of China
| | - He Ren
- Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 People’s Republic of China
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Formica V, Morelli C, Ferroni P, Nardecchia A, Tesauro M, Pellicori S, Cereda V, Russo A, Riondino S, Guadagni F, Roselli M. Neutrophil/lymphocyte ratio helps select metastatic pancreatic cancer patients benefitting from oxaliplatin. Cancer Biomark 2017; 17:335-345. [PMID: 27434293 DOI: 10.3233/cbm-160645] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND High Neutrophil/Lymphocyte ratio (NLR), as a measure of enhanced inflammatory response, has been negatively associated with prognosis in patients with localized pancreatic ductal adenocarcinoma (PDA). OBJECTIVE In the present study, we aimed at investigating the prognostic value of NLR in two homogeneous groups of chemotherapy-naïve metastatic PDA patients. Patients were treated with either gemcitabine (GEM) or gemcitabine/oxaliplatin (GEMOXA). We also assessed whether NLR could identify patients benefiting from the use of oxaliplatin. METHODS Consecutive PDA patients treated at the Medical Oncology Unit of Tor Vergata University Hospital of Rome with either GEM or GEMOXA were included (n= 103). NLR was assessed before and during chemotherapy and correlated with outcome together with common clinical and biochemical variables. RESULTS Among 17 analyzed variables NLR, Karhofsky Perfomance Status (KPS), d-dimer and erythrocyte sedimentation rate were found to be significantly associated with median Overall Survival (mOS) at the univariate analysis. Only NLR and KPS were independent prognosticator at multivariate analysis, with NLR displaying the highest statistical significance. NLR was also predictive of oxaliplatin activity, as only patients with NLR > 2.5 (cutoff determined upon ROC analysis) derived benefit from GEMOXA over GEM. CONCLUSIONS NLR is both an independent prognostic and predictive factor in metastatic PDA, since only patients with high NLR seem to benefit from the addition of oxaliplatin. NLR may help select patients for whom a particularly poor prognosis might justify more intensive, yet less tolerable, combination regimens.
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Affiliation(s)
- Vincenzo Formica
- Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy
| | - Cristina Morelli
- Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy
| | - Patrizia Ferroni
- San Raffaele Roma Open University, Rome, Italy.,Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy
| | - Antonella Nardecchia
- Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy
| | - Manfredi Tesauro
- Department of Systems Medicine, Internal Medicine, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy
| | - Stefania Pellicori
- Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy
| | - Vittore Cereda
- Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy
| | - Antonio Russo
- Section of Medical Oncology, Department of Surgical and Oncology Sciences, University of Palermo, Italy
| | - Silvia Riondino
- Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy.,Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy
| | - Fiorella Guadagni
- San Raffaele Roma Open University, Rome, Italy.,Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy
| | - Mario Roselli
- Department of Systems Medicine, Medical Oncology, Tor Vergata Clinical Center, Tor Vergata University of Rome, Rome, Italy
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Desch A, Gebhardt C, Utikal J, Schneider SW. D-dimers in malignant melanoma: Association with prognosis and dynamic variation in disease progress. Int J Cancer 2016; 140:914-921. [PMID: 27813063 DOI: 10.1002/ijc.30498] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Revised: 10/07/2016] [Accepted: 10/24/2016] [Indexed: 02/05/2023]
Abstract
Malignant cells elicit a chronic hemostatic activation in disease progress. This procoagulant activity does not only bear a risk for thromboembolism but also facilitates tumor growth and dissemination. An elevated plasma D-dimer level indicates an activated coagulation and fibrinolysis. In this study, the association of D-dimer levels with clinicopathological parameters and patients outcome in melanoma was investigated analyzing in total 533 melanoma patients retrospectively. Using the cut-off point of 0.6 mg/L D-dimer 145 of the total 533 patients (27.2%) were identified with elevated plasma D-dimer levels. This increased D-dimer level positively correlated with tumor thickness (p = 0.0003), lymph node invasion (p = 0.0004) and metastatic state (p <0.0001). To assess the association of D-dimer levels with progression-free survival (PFS) and overall survival (OS), long-rank test and the Cox proportional hazard model was performed. Univariate analyses revealed that elevated D-dimer levels were significantly associated with decreased PFS (HR:2.89, 95% CI (2.07-7.56), p < 0.0001) and OS (HR:2.22, 95% CI (1.06-4.57), p = 0.035). Moreover, multivariate analyses identified elevated D-dimer levels being associated with poor disease outcome (PFS:HR:2.47, 95% CI (1.23-4.98), p = 0.012; OS:HR:2.01, 95% CI (0.09-4.45), p = 0.087). Additionally, D-dimer levels were significantly increased in terminal stage patients when comparing plasma levels 0-8 versus 24-48 weeks before death (p = 0.0003). In summary, this study presents multiple evidence that elevated D-dimer levels in melanoma patients associate with poor prognosis and therefore plasma levels of D-dimers could reveal a more aggressive phenotype of melanoma and may guide the management of anti-melanoma treatment including the concept of an anti-coagulatory therapy in tumor patients.
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Affiliation(s)
- Anna Desch
- Experimental Dermatology, Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany
| | - Christoffer Gebhardt
- Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.,Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jochen Utikal
- Department of Dermatology, Venereology, and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.,Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Stefan W Schneider
- Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany
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Kanda M, Tanaka C, Kobayashi D, Mizuno A, Tanaka Y, Takami H, Iwata N, Hayashi M, Niwa Y, Yamada S, Fujii T, Sugimoto H, Murotani K, Fujiwara M, Kodera Y. Proposal of the Coagulation Score as a Predictor for Short-Term and Long-Term Outcomes of Patients with Resectable Gastric Cancer. Ann Surg Oncol 2016; 24:502-509. [PMID: 27600621 DOI: 10.1245/s10434-016-5544-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Systemic hemostasis and thrombosis activation has been implicated in tumor progression and metastasis. This study aimed to investigate the use of coagulation factors as a novel prediction method for postoperative outcomes after curative gastrectomy in patients with stage II/III gastric cancer (GC). METHODS Overall, 126 patients with stage II/III GC who underwent gastrectomy between May 2003 and February 2016 were eligible for inclusion in the study. We retrospectively evaluated the predictive value of preoperative platelet count and plasma fibrinogen and d-dimer levels, and coagulation score (0: fibrinogen and d-dimer both below upper limits; 1: either fibrinogen or d-dimer over upper limits; 2: both fibrinogen and d-dimer over upper limits) for short- and long-term outcomes. RESULTS Postoperative complications were significantly more frequent in patients with elevated preoperative d-dimer levels compared with those with normal d-dimer levels (26 vs. 10 %; p = 0.032). The prevalence of postoperative complications showed a stepwise increase in proportion to the coagulation score. Patients with a coagulation score of 2 had significantly larger tumors (p = 0.013) and significantly greater intraoperative blood loss (p = 0.004) than those who scored 0 or 1. Coagulation score showed the highest values distinguished high-risk patients in overall and disease-free survival, and a coagulation score of 2 was an independent prognostic factor for recurrence. Patients with a coagulation score of 2 experienced a significantly higher prevalence of liver metastasis as an initial recurrence than those who scored 0 or 1 (p = 0.019). CONCLUSIONS The coagulation score is a simple and promising predictor for postoperative complications and recurrence after gastrectomy in stage II/III GC patients.
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Affiliation(s)
- Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Daisuke Kobayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akira Mizuno
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuri Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hideki Takami
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Naoki Iwata
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masamichi Hayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yukiko Niwa
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Suguru Yamada
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tsutomu Fujii
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroyuki Sugimoto
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Murotani
- Center for Clinical Research, Aichi Medical University, Nagakute, Japan
| | - Michitaka Fujiwara
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
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Wang L, Sheng L, Liu P. The independent association of platelet parameters with overall survival in pancreatic adenocarcinoma receiving intensity-modulated radiation therapy. Int J Clin Exp Med 2015; 8:21215-21221. [PMID: 26885057 PMCID: PMC4723902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Accepted: 11/06/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND Platelets are involved in multiple links of the process of thrombus formation and development. The aim of this study is to investigate the impact of pretreatment platelet parameters, such as plateletcrit (PCT), platelet mean distribution width (MDW), and mean platelet volume (MPV) in a cohort of patients with locally advanced pancreatic adenocarcinoma treated with a combination of chemotherapy and radiation therapy. METHODS A retrospective analysis was conducted of 163 locally advanced unresectable consecutive pancreatic adenocarcinoma patients who received chemoradiotherapy in Zhejiang cancer hospital from January 2009 to December 2011. The effects of platelet parameters on overall survival (OS) were assessed using Kaplan-Meier analysis. Independent prognostic factors were identified in the multivariate Cox analysis. RESULTS The median of the PC, PCT, MDW, MPV and CRP were 175×10(9), 20.0%, 14.0%, 10.8 fl and 7.0 mg/L, respectively. MDW was positively correlated with PC (r=0.156, P=0.047) and CRP (r=0.591, P<0.001). The median survival time of high MDW group was significantly worse than that of low MDW group (14.0 m Vs 11.0 m, P=0.008). Patients with high PCT were found to have shorter overall survival time (15.0 m Vs 11.0 m, P=0.018). Multivariate analysis indicated that MDW and N stage were two independent prognostic factors for overall survival (P<0.05). Patients with higher MDW had a 1.48-fold increased risk of death compared to those with low MDW. CONCLUSIONS MDW is an independent negative prognostic factor for overall survival in pancreatic adenocarcinoma patients.
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Affiliation(s)
- Lei Wang
- Department of Radiotherapy, Zhejiang Cancer Hospital Hangzhou, Zhejiang, China
| | - Liming Sheng
- Department of Radiotherapy, Zhejiang Cancer Hospital Hangzhou, Zhejiang, China
| | - Peng Liu
- Department of Radiotherapy, Zhejiang Cancer Hospital Hangzhou, Zhejiang, China
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