Implication of Hepsin from primary tumor in the prognosis of colorectal cancer patients

Author:

Zaragoza-Huesca DavidORCID,Nieto-Olivares Andrés,García-Molina FranciscoORCID,Ricote Guillermo,Montenegro SofíaORCID,Sánchez-Cánovas Manuel,Garrido-Rodríguez PedroORCID,Peñas-Martínez JuliaORCID,Vicente VicenteORCID,Martínez Francisco,Luisa-Lozano María,Carmona-Bayonas AlbertoORCID,Martínez-Martínez IreneORCID

Abstract

ABSTRACTBackgroundHepsin is a type II transmembrane serine protease whose functions include degradation of the extracellular matrix and activation of factor VII. In many tumors, hepsin dysregulation leads to tumor invasion by proteolysis of pericellular components. Colorectal cancer is a tumor with high thrombotic and metastatic risk, but the role of hepsin is unknown.ObjectivesTo study the correlations between hepsin expression in the primary tumor and different clinical-histopathological variables in patients with localized and metastatic colorectal cancer.MethodsA cohort of 287 patients, 169 with localized colorectal cancer and 118 with metastases at diagnosis, was recruited. Tissue microarrays were made from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin levels were determined and the association with clinical-histopathological variables was evaluated using the chi-square and Kruskal-Wallis tests. Time-to-event results and cumulative incidence functions were calculated using Kaplan-Meier and Aalen-Johansen estimators, in combination with Cox and Fine&Gray multivariate models.ResultsIn patients with localized colorectal cancer, high intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). In this context, according to multivariable Cox regression, medium and high intensity of hepsin expression versus low intensity was associated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value=0.035, and hazard ratio 3.30, p-value=0.012, respectively), being a more accurate prognostic factor than classic histological variables. Also, in patients with localized colorectal cancer, the cumulative incidence of thrombosis at 5 years increased significantly with higher hepsin levels (p-value = 0.038). According to the multivariate Fine&Gray regression, the medium and high intensity of hepsin with respect to the low intensity, was associated with an increase in thrombotic risk (hazard ratio 7.71, p-value=0.043 and hazard ratio 9.02, p-value=0.028, respectively). This relationship between hepsin and thrombosis was independent of previous tumor relapse (p-value = 0.036). In patients with metastatic colorectal cancer, low intensity of hepsin was associated with a low degree of tumor differentiation (p-value <0.001) and spread to more than one metastatic site (p-value = 0.023).ConclusionHepsin is a potential biomarker of thrombosis and metastasis in patients with localized colorectal cancer. Validation in a larger series and clarification of the underlying mechanism may be helpful in evaluating these patients. In metastatic patients, Hepsin behaves in a paradoxical way with respect to differentiation and invasion processes.

Publisher

Cold Spring Harbor Laboratory

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3