PB0782 - Hepsin is a risk factor for thrombosis and metastasis in localized colorectal cancer patients

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

David Zaragoza Huesca, PhD student

PhD student
Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla
Murcia, Murcia, Spain

Co-Author(s)

AN

Andrés Nieto Olivares

PhD
Department of Pathology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Murcia, Murcia, Spain
FG

Francisco García Molina

PhD
Department of Pathology, Hospital Universitario Reina Sofía, Murcia, Spain.
Murcia, Murcia, Spain
GR

Guillermo Ricote Sánchez

Medical Doctor
Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
Murcia, Murcia, Spain
MS

Manuel Sánchez Cánovas

PhD
Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30003 Murcia, Spain.
Murcia, Murcia, Spain
AM

Alberto Martínez

Laboratory technician
Department of Pathology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Murcia, Murcia, Spain
Pedro Garrido-Rodríguez

PhD Student
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer-Centro Regional de Hemodonación, Universidad de Murcia, IMIB, CIBERER Spain
Murcia, Murcia, Spain
JP

Julia Peñas-Martínez

PhD student
Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
Murcia, Murcia, Spain
SM

Sofía Montenegro Luis

Medical Doctor
Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
Murcia, Murcia, Spain
VV

Vicente Vicente

Researcher and Medical Doctor
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER, Murcia, Spain
Murcia, Murcia, Spain
AC

Alberto Carmona Bayonas

Medical Doctor
Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, CIBERER, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
Murcia, Murcia, Spain
Irene Martínez Martínez, PhD

Principal Investigator
Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla
Murcia, Murcia, Spain

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.