Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients
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-hi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/13/3106 |
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| author | David Zaragoza-Huesca Andrés Nieto-Olivares Francisco García-Molina Guillermo Ricote Sofía Montenegro Manuel Sánchez-Cánovas Pedro Garrido-Rodríguez Julia Peñas-Martínez Vicente Vicente Francisco Martínez María Luisa Lozano Alberto Carmona-Bayonas Irene Martínez-Martínez |
| author_facet | David Zaragoza-Huesca Andrés Nieto-Olivares Francisco García-Molina Guillermo Ricote Sofía Montenegro Manuel Sánchez-Cánovas Pedro Garrido-Rodríguez Julia Peñas-Martínez Vicente Vicente Francisco Martínez María Luisa Lozano Alberto Carmona-Bayonas Irene Martínez-Martínez |
| author_sort | David Zaragoza-Huesca |
| collection | DOAJ |
| description | 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 (<i>p</i>-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, <i>p</i>-value = 0.035 and hazard ratio 3.30, <i>p</i>-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 (<i>p</i>-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, <i>p</i>-value = 0.043 and hazard ratio 9.02, <i>p</i>-value = 0.028, respectively). This relationship was independent of previous tumor relapse (<i>p</i>-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (<i>p</i>-value < 0.001) and with major metastatic dissemination (<i>p</i>-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. |
| first_indexed | 2024-03-09T22:03:13Z |
| format | Article |
| id | doaj.art-13cf59e38d7a446fab18c4e06affc88c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:03:13Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-13cf59e38d7a446fab18c4e06affc88c2023-11-23T19:44:33ZengMDPI AGCancers2072-66942022-06-011413310610.3390/cancers14133106Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer PatientsDavid Zaragoza-Huesca0Andrés Nieto-Olivares1Francisco García-Molina2Guillermo Ricote3Sofía Montenegro4Manuel Sánchez-Cánovas5Pedro Garrido-Rodríguez6Julia Peñas-Martínez7Vicente Vicente8Francisco Martínez9María Luisa Lozano10Alberto Carmona-Bayonas11Irene Martínez-Martínez12Centro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainDepartment of Pathology, Hospital General Universitario Morales Meseguer, 30008 Murcia, SpainDepartment of Pathology, Hospital General Universitario Reina Sofía, 30003 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainDepartment of Pathology, Hospital General Universitario Reina Sofía, 30003 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainCentro Regional de Hemodonación, Department of Haematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB-Arrixaca, 30100 Murcia, SpainHepsin 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 (<i>p</i>-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, <i>p</i>-value = 0.035 and hazard ratio 3.30, <i>p</i>-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 (<i>p</i>-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, <i>p</i>-value = 0.043 and hazard ratio 9.02, <i>p</i>-value = 0.028, respectively). This relationship was independent of previous tumor relapse (<i>p</i>-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (<i>p</i>-value < 0.001) and with major metastatic dissemination (<i>p</i>-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.https://www.mdpi.com/2072-6694/14/13/3106hepsincolorectal cancerthrombosismetastasishepsin paradox |
| spellingShingle | David Zaragoza-Huesca Andrés Nieto-Olivares Francisco García-Molina Guillermo Ricote Sofía Montenegro Manuel Sánchez-Cánovas Pedro Garrido-Rodríguez Julia Peñas-Martínez Vicente Vicente Francisco Martínez María Luisa Lozano Alberto Carmona-Bayonas Irene Martínez-Martínez Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients Cancers hepsin colorectal cancer thrombosis metastasis hepsin paradox |
| title | Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients |
| title_full | Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients |
| title_fullStr | Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients |
| title_full_unstemmed | Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients |
| title_short | Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients |
| title_sort | implication of hepsin from primary tumor in the prognosis of colorectal cancer patients |
| topic | hepsin colorectal cancer thrombosis metastasis hepsin paradox |
| url | https://www.mdpi.com/2072-6694/14/13/3106 |
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