Colorectal Cancer in Correlation With Clinicopathological Variables: The Effects of Hypoxia-Inducible Factor-1 Alfa or the InterLeukin-33 and Vascular Endothelial Growth Factor?

Background The hypoxia-inducible factor-1 alpha (HIF-1 alpha) is believed to control angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the interLeukin-33 (IL-33) gene and vascular endothelial growth factor (VEGF) gene. The study aimed to study the HIF-1 alpha and its two hypoxia pathway genes; IL-33 and VEGF, together with the angiogenesis and correlate them with some prognostic clinicopathological features, separately and in combination to assess their dependency. Methodology This study included 87 colorectal cancer (CRC) cases, diagnosed between January 2019 and December 2022. Different prognostic clinicopathological features were examined and tissue microarray (TMA) slides were designed to carry out IHC for IL-33 and VEGF scoring in tumor cells, in addition to qualitative interpretation of VEGF expression in tumor vessels. Molecular analysis was performed for HIF-1 alpha and all data were correlated to the clinicopathological features, separately and collectively, to assess the dependency of these factors. Results No statistical correlation could be seen among the IL-33, VEGF, and prognostic clinicopathological features. Whereas analysis of the HIF-1 alpha alone showed significantly high mean expression in patients with distance metastasis and was increased with the increased involvement of the lymph nodes (LNs). However, when the HIF 1-alpha expression was correlated with the clinicopathological characteristics on the bases of VEGF and IL 33 expressions the significant association with metastasis disappeared in tumor cells and appeared only with the endothelium of the tumor angiogenesis. Moreover, the results conflicted with the LNs involvement. Conclusions These findings may suggest a role of HIF 1-alpha in the downstream regulation of biomarkers other than the VEGF and IL-33, which needs to uncover pathways and novel factors regulated by the HIF 1-alpha for the proinflammation and angiogenesis in malignancy.