Abstract Number: PB0782
Meeting: ISTH 2022 Congress
Theme: Hemostatic Systems in Cancer, Inflammation and Immunity » Proteases and Cancer
Background: Hepsin (HPN) is a transmembrane serine-protease which functions include extracellular matrix degradation and factor VII activation. In cancer, HPN dysregulation leads to tumor invasion by proteolysis of pericellular components. Colorectal cancer (CRC) relates to high thrombotic and metastatic risk, but HPN role is unknown.
Aims: To study correlations between primary tumor HPN expression and clinical-histopathological variables of localized and metastatic CRC patients.
Methods: We recruited 287 patients, 169 with localized and 118 with metastatic CRC at diagnosis. Two-millimeter diameter sections from primary tumor diagnostic biopsies were obtained to prepare tissue microarrays (TMAs), which were stained with an anti-HPN antibody. HPN expression levels were determined by two independent pathologists, and finally, the association with clinical-histopathological variables was assessed by chi-square tests, One-way Anova models and Kruskal-Wallis tests. Time-to-event results were estimated using Kaplan-Meier or competing risk-sensitive estimators.
Results: In localized CRC patients, elevated HPN levels independently increased the incidence of thrombosis and metastasis (Figure 1). By pairwise comparison, differences were significant between high and low HPN levels for both thrombosis and metastasis (p-value=0.006 and 0.008, respectively). Five-year thrombosis-free survival was 76% (64%-89.4%, 95% CI), 89% (80%-98.6%, 95% CI) and 100% (100%-100%, 95% CI) for patients with high, medium and low HPN levels, respectively. Five-year metastasis-free survival was 52.9% (39.5%-71%, 95% CI), 62.6% (49.3%-79.6%, 95% CI) and 78.2% (61.8%-99%, 95% CI) for patients with high, medium and low HPN levels, respectively. Regarding metastatic CRC patients, we found HPN levels significantly increased (p-value=2.55E-06) when tumor reached a moderate differentiation respecting healthy tissue, but this expression was dramatically lost when cancer reached its maximum differentiation (poorly differentiated) (Figure 2), which could indicate that HPN is necessary just for early differentiation steps.
Conclusion(s): HPN constitutes a potential biomarker for thrombosis and metastasis in localized CRC patients. Validation in a larger series could help to assess these patients.
To cite this abstract in AMA style:
Zaragoza Huesca D, Nieto Olivares A, García Molina F, Ricote Sánchez G, Sánchez Cánovas M, Martínez A, Garrido-Rodríguez P, Peñas-Martínez J, Montenegro Luis S, Vicente V, Carmona Bayonas A, Martínez Martínez I. Hepsin is a risk factor for thrombosis and metastasis in localized colorectal cancer patients [abstract]. https://abstracts.isth.org/abstract/hepsin-is-a-risk-factor-for-thrombosis-and-metastasis-in-localized-colorectal-cancer-patients/. Accessed March 21, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/hepsin-is-a-risk-factor-for-thrombosis-and-metastasis-in-localized-colorectal-cancer-patients/