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      High pretreatment plasma D-dimer predicts poor survival of colorectal cancer: insight from a meta-analysis of observational studies

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          Abstract

          D-dimer, one of the canonical markers of hypercoagulability, was reported to be a potential prognostic marker of colorectal cancer. However, an inconsistent conclusion existed in several published studies. Thus, we performed this meta-analysis to provide a comprehensive insight into the prognostic role for pretreatment D-dimer in colorectal cancer. Six databases (English: Pubmed, Embase and Web of Science; Chinese: CNKI, Wangfang and VIP) were utilized for the literature retrieval. Hazard ratio (HR) was pooled by Stata 12.0. A total of fifteen studies (2283 cases) corresponded to this meta-analysis and provided available data to evaluate the prognostic role of D-dimer for colorectal cancer. The pooled HR reached 2.167 (95%. CI (confidence interval): 1.672–2.809, P < 0.001) utilizing random effect model due to obvious heterogeneity among the included studies (I 2: 73.3%; P < 0.001). To explore the heterogeneity among the studies, we conducted a sensitivity analysis and found a heterogeneous study. After removing it, the heterogeneity reduced substantially (I 2: 0%; P = 0.549) and we obtained a more convincing result by fixed effect model (HR = 2.143, 95% CI = 1.922–2.390, P < 0.001, 14 studies with 2179 cases). In summary, high pretreatment plasma D-dimer predicts poor survival of colorectal cancer based on the current evidence. Further prospective researches are necessary to confirm the role of D-dimer in colorectal cancer.

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          Most cited references30

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          Coagulation and cancer: biological and clinical aspects.

          Malignancy affects the hemostatic system and the hemostatic system affects malignancy. In cancer patients there are a number of coagulation abnormalities which provide the background for an increased tendency of these patients to both thrombosis and hemorrhage. The causes of this coagulation impairment rely on general risk factors which are common to other categories of patients, and other factors which are specific to cancer, such as tumor type and disease stage. In addition, data from basic research indicate that the hemostatic components and the cancer biology are interconnected in multiple ways. Notably, while cancer cells are able to activate the coagulation system, the hemostatic factors play a role in tumor progression. This opens the way to the development of bifunctional therapeutic approaches that are both capable of attacking the malignant process and resolving the coagulation impairment. On the other hand, the management of thrombosis and hemorrhages in cancer patients can be different. To approach these problems, some guidelines have been released by prominent international scientific societies. Also actively investigated is the issue of identifying new biomarkers to classify the subjects at a higher risk, thus improving the prevention of thrombohemorrhagic events in these patients. Finally, novel prophylactic and therapeutic approaches are currently under development. This review provides an overview of the hemostatic complications in cancer, together with new insights into the interaction between hemostasis and cancer biology. We also review the assessment of the risk of thrombohemorrhagic events in cancer patients, and the prophylaxis and treatment of such manifestations. © 2012 International Society on Thrombosis and Haemostasis.
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            Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis.

            Tissue factor (TF) is the primary cellular initiator of blood coagulation and a modulator of angiogenesis and metastasis in cancer. Indeed, systemic hypercoagulability in patients with cancer and TF overexpression by cancer cells are both closely associated with tumor progression, but their causes have been elusive. We now report that in human colorectal cancer cells, TF expression is under control of 2 major transforming events driving disease progression (activation of K-ras oncogene and inactivation of the p53 tumor suppressor), in a manner dependent on MEK/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase (PI3K). Furthermore, the levels of cell-associated as well as circulating (microvesicle-associated) TF activity are linked to the genetic status of cancer cells. Finally, RNA interference experiments suggest that TF expression is an important effector of the K-ras-dependent tumorigenic and angiogenic phenotype in vivo. Thus, this study establishes a causal link between cancer coagulopathy, angiogenesis, and genetic tumor progression.
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              High preoperative plasma D-dimer level is associated with advanced tumor stage and short survival after curative resection in patients with colorectal cancer.

              An elevated plasma D-dimer level indicates activation of coagulation and fibrinolysis. Previous studies demonstrated that the preoperative plasma D-dimer level correlates with tumor stage in patients with colorectal cancer. This study examined the relationship between preoperative plasma D-dimer level and both pathological findings and TNM classification and examined the prognostic significance of preoperative plasma D-dimer level. Preoperative plasma D-dimer levels were measured in 93 patients who underwent curative resection of colorectal cancer and 40 patients with benign colorectal diseases other than inflammatory bowel disease. The results were analyzed for correlations between preoperative plasma D-dimer levels in patients with colorectal cancer and pathological findings, TNM classification and postoperative survival. Preoperative plasma D-dimer levels were significantly higher in patients with colorectal cancer than in patients with benign colorectal diseases. Plasma D-dimer levels were higher in patients with tumors that were relatively large, had relatively deep wall penetration and were at a relatively advanced TNM stage. Higher preoperative plasma D-dimer levels were significantly associated with shorter postoperative overall survival. Results of analysis with a multivariate proportional hazard model suggested that preoperative plasma D-dimer level was the third strongest prognostic factor; exceeded in importance only by lymph node status and preoperative carcinoembryonic antigen level. Elevated plasma D-dimer levels in patients with colorectal cancer are associated with relatively advanced tumor stage and short postoperative survival after curative resection. It appears that measurement of preoperative D-dimer level would be useful in the preoperative diagnosis of tumor stage and prediction of postoperative survival.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                6 October 2017
                15 September 2017
                : 8
                : 46
                : 81186-81194
                Affiliations
                1 Department of Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
                2 Department of Emergency, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China
                Author notes
                Correspondence to: Wei-Zhong Tang, tangweizhong0771@ 123456163.com
                Article
                20919
                10.18632/oncotarget.20919
                5655273
                29113378
                5e12548f-102c-4338-9501-460e799dee0a
                Copyright: © 2017 Lu et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 16 June 2017
                : 26 August 2017
                Categories
                Meta-Analysis

                Oncology & Radiotherapy
                d-dimer,prognosis,colorectal cancer
                Oncology & Radiotherapy
                d-dimer, prognosis, colorectal cancer

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