Research Laboratory, IIIrd Department of Internal Medicine, MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
Department of Hematology and Stem Cell Transplantation, United St. Istvan and St. Laszlo Hospital, Budapest, Hungary.
Thromb Haemost. 2018 Jan;118(1):123-131. doi: 10.1160/TH17-07-0548. Epub 2018 Jan 5.
Distant metastasis is a major cause of colorectal cancer-related death, but the mechanism of tumour progression is not fully understood. There is growing evidence of an interaction between tumour cells and platelets which may influence tumour progression and metastasis formation. Quality and quantity of von Willebrand factor may regulate the interaction between tumour cells and platelets. Our aim was to measure the platelet count, von Willebrand factor antigen (VWF:Ag) levels and ADAMTS13 activity in a large ( = 232) cohort of colorectal cancer patients and to examine their relationships with the stage of the disease and 5-year survival without thrombotic complications using multivariable models. Significantly higher platelet counts ( = 0.005), VWF:Ag levels ( = 0.008) and decreased ADAMTS13 activity ( = 0.006) were observed in patients with metastatic disease. Results of the Kaplan-Meier analysis showed that lower platelet counts ( < 0.0001), lower VWF:Ag ( = 0.0008) levels and higher ADAMTS13 activity ( < 0.0001) were associated with better event-free survival. Finally, to investigate the association between overall event-free survival and the three study variables, multivariate Cox proportional hazard models were generated. All models were adjusted for age, gender and disease stage. Platelet count, ADAMTS13 activity or VWF:Ag level were incorporated and all of these variables turned out to be age-, gender- and stage-independent predictors of mortality (all hazard ratio >1.7, < 0.05). In summary, this is the first observational study reporting association between higher mortality or thrombotic complications and increased platelet count, increased VWF:Ag levels and decreased ADAMTS13 activity in colorectal cancer.
远处转移是结直肠癌相关死亡的主要原因，但肿瘤进展的机制尚不完全清楚。越来越多的证据表明肿瘤细胞与血小板之间存在相互作用，这可能影响肿瘤的进展和转移形成。血管性血友病因子（von Willebrand factor，VWF）的质量和数量可能调节肿瘤细胞与血小板之间的相互作用。我们的目的是在一个较大的（ = 232）结直肠癌患者队列中测量血小板计数、血管性血友病因子抗原（von Willebrand factor antigen，VWF:Ag）水平和 ADAMTS13 活性，并使用多变量模型检查它们与疾病分期和 5 年无血栓并发症生存的关系。转移性疾病患者的血小板计数（ = 0.005）、VWF:Ag 水平（ = 0.008）和 ADAMTS13 活性（ = 0.006）显著升高。Kaplan-Meier 分析结果表明，较低的血小板计数（ < 0.0001）、较低的 VWF:Ag 水平（ = 0.0008）和较高的 ADAMTS13 活性（ < 0.0001）与无事件生存相关。最后，为了研究总无事件生存率与三个研究变量之间的关系，我们生成了多变量 Cox 比例风险模型。所有模型均调整了年龄、性别和疾病分期。血小板计数、ADAMTS13 活性或 VWF:Ag 水平被纳入模型，所有这些变量都是年龄、性别和分期独立的死亡预测因素（所有危险比 >1.7， < 0.05）。总之，这是第一项观察性研究报告结直肠癌患者血小板计数升高、VWF:Ag 水平升高和 ADAMTS13 活性降低与更高的死亡率或血栓并发症之间存在关联。
