Relationship of HIF-1α/LOX/ITGA5 protein expression associated with extracellular matrix regulation with prognostic and molecular features in colorectal carcinomas

Colorectal cancers are heterogeneous tumors from a histopathological and molecular perspective. In order to determine the most appropriate personalized treatment, it is necessary to take into account the characteristics of the tumor as well as the tumor microenvironment which is becoming increasingly important in relation to angiogenesis, invasion, metastasis and treatment. In this study, stromal and tumoral expression of hypoxia-associated HIF-1α/LOX/ITGA5 proteins, which have been reported to be associated with prognosis and treatment resistance were determined by clinicopathological prognostic parameters, KRAS/NRAS/BRAF mutation, status in CRCs. 100 cases whose resection materials were evaluated at Ankara City Hospital Pathology Clinic between 2019 and 2021 and whose KRAS/NRAS/BRAF mutation analysis and MMR status were examined were included. Immunohistochemical staining for HIF-1α, ITGA5 and LOX was performed on tissue microarray blocks. Staining intensity was compared with histopathological and prognostic variables. A positive correlation was detected between the stromal expression intensity of HIF-1α/LOX/ITGA5 proteins and tumoral HIF-1α and LOX expression. The number of metastatic lymph nodes was found to be higher in patients with KRAS/NRAS/BRAF mutation and moderate-to-strong expression of all three of these proteins in the tumor stroma than in other patients. In stage 4 patients, those with moderate-to-strong expression of HIF-1α, ITGA5 or LOX in the tumor microenvironment were found to have lower progression-free survival than those with mild expression. Additionally, female gender, moderate-to-strong HIF-1α/LOX/ITGA5 stromal expression, and metastatic 1st-line chemotherapy alone were independently associated with increased risk of progression. In metastatic patients under treatment; The detection of a significant relationship between stromal expression of HIF-1α/LOX/ITGA5 and a decrease in progression-free survival also suggests that these markers may be useful in predicting response or resistance treatment. Our study should be supported by more comprehensive studies addressing tumor stroma and its prognostic importance.