title: D-dimer is an essential accompaniment of circulating tumor cells in gastric cancer.
abstract: 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.
  
  
  
  We 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.
  
  
  
  In 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.
  
  
  
  Plasma 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.
authors.affiliation: Oncology Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Diao
authors.affiliation: Thoracic Surgery Department, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Oncology Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Song
authors.affiliation: Oncology Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Oncology Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Oncology Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, People's Republic of China. dangchengxue@mail.xjtu.edu.cn.
authors.forename: Chengxue
authors.initials: C
authors.lastname: Dang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005340:Fibrinogen
keywords: Circulating tumor cells (CTCs); D-dimer; Gastric cancer (GC); Metastasis; Outcome