Expression analysis of HIF-3a as a potent prognostic biomarker in various types of human cancers: a case of meta-analysis

Abstract

Background and purpose: Hypoxia-inducible factors (HIFs) are transcription factors that get activated and stabilized in the heterodimerized form under hypoxic conditions. many studies have reported the importance of the HIF-1 alpha and HIF-2 alpha activity in biological pathways of hypoxic cancer cells. However, the importance of HIF-3 alpha in a variety of cancers remains unknown. Experimental approach: The expression profile of 13 different types of cancer samples from the Cancer Genome Atlas (TCGA) database were subjected to normalization, and differential gene expression analysis was performed using computational algorithms by R programming. Receiver operating characteristic tests and survival analyses were carried out for HIF-alpha subunits in different cancers. Findings / Results: The expression status of HIF-3 alpha was notably less in all cancer samples in contrast to their adjacent normal tissues. The expression degree of HIF-1 alpha varied among distinct types of cancer and the expression degree of HIF-2 alpha was lower in nearly all types of cancers. HIF-3 alpha had very weak diagnostic potential, while HIF-2 alpha had better diagnostic potential in most types of cancers compared to HIF-1 alpha. Patients who had a higher level of HIF-3 alpha had better survival, while the higher expression level of HIF-1 alpha and HIF-2 alpha were associated with worse survival in many types of cancers. Conclusion and implications: Our findings showed that each HIF-alpha subunit had a unique heterogeneous expression pattern in different classes of cancers. The expression level of each HIF-alpha subunit correlated differently with the stages, tumor sizes, and survival rate of patients from different classes of TCGA cancers.