D-dimer is an essential accompaniment of circulating tumor cells in gastric cancer

Dongmei Diao,Zhangjian Zhou,Yongchun Song,Yao Cheng,Hao Zhang,Chengxue Dang

doi:10.1186/s12885-016-3043-1

Abstract

BackgroundFibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it’s stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients.MethodsWe first verified our hypothesis in different murine gastric cancer metastasis models in vivo, plasma D-dimer and fibrinogen as well as its degradation products were directly examined in three metastasis immune-deficient mouse models and in controls. Next, we gathered and analyzed the result of plasma D-dimer levels and CTCs numbers in 41 advanced primary gastric cancer (GC) patients. A follow-up study was conducted in these patients.ResultsIn three in vivo murine metastasis models, plasma D-dimer levels were extremely elevated in a hematogenous and intraperitoneal murine model of metastasis compared with a subcutaneous tumor model and the control group, supporting our previous hypothesis. While in 41 GC patients, the result displayed that plasma D-dimer levels were remarkably increased in patients with distant metastases, especially in visceral metastases patients. Additionally, linear association was shown between D-dimer level and CTCs numbers (R2 = 0.688, p < 0.001), additionally, plasma D-dimer represent a better survival predictor than CTCs.ConclusionsPlasma D-dimer is an essential accompaniment of CTCs in GC that is easy to measure and lower in cost, and can be used in the detection of hematogenous metastasis.

Highlights

Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development
FIB is essential in CTCs survival, but not strong in clinical use to detect metastasis, but D-dimer revealed its advantages in this field
We first verified that plasma Ddimer are significantly increased in a metastasis model in vivo especially in hematogenous metastasis, underlying D-dimer increased when CTCs spread into the vascular, this factor reflect cancer metastasis and might be an accompaniment for CTCs of gastric cancer (GC)

Summary

Introduction

Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it’s stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients. D-dimer, the final stable product of fibrin, which elevated after enhanced activation of Coagulation and fibrinolysis system, widely used in detect and exclude deep vein thrombosis and associated thromboembolic diseases [6,7,8]. FIB is essential in CTCs survival, but not strong in clinical use to detect metastasis, but D-dimer revealed its advantages in this field. It may be associated with CTCs appearance and can reflect the metastatic phenotype of caner patients

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Discussion

Conclusion