Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients

Simple Summary Hepsin is a serine protease whose deregulation leads to tumor invasion and metastasis in many tumor types. In colorectal cancer, the role of hepsin is unknown, so we aimed to study the correlations between its expression and clinical-histopathological variables of patients with this cancer. We recruited 169 patients with localized disease and 118 with metastatic cancer at diagnosis, and then, we measured hepsin staining from primary biopsy in order to correlate it with time-to-event variables, laboratory data, genetic alterations, histologic features, etc. Our results demonstrated hepsin was an independent prognosis factor for metastasis and thrombosis in patients with localized disease, whereas among metastatic subjects, lower levels of hepsin were associated with highest tumor dedifferentiation and spread to distant organs. These results point to hepsin as a potential biomarker for considerable complications in patients with colorectal cancer. In addition, this article brings to light new information about the implication of hepsin in colorectal cancer. Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical-histopathological variables by using the chi-square and Kruskal-Wallis tests, Kaplan-Meier and Aalen-Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression 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 better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were 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 was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical way with respect to differentiation and invasion processes.

Automated summary

This study investigated the role of hepsin in colorectal cancer and found that it is an independent prognostic factor for metastasis and thrombosis in patients with localized disease. Low levels of hepsin were associated with higher tumor dedifferentiation and spread to distant organs in metastatic patients. These findings suggest that hepsin could be a potential biomarker for complications in colorectal cancer patients.