HIF1α: A Novel Biomarker with Potential Prognostic and Immunotherapy in Pan-cancer

Cancer is a catastrophic disease that seriously affects human health. HIF1 alpha plays an important role in cancer initiation, progression, and prognosis. However, little is known about the specific role of HIF1 alpha in pan-cancer. Therefore, we systematically and comprehensively analyzed HIF1 alpha using GEPIA, HPA, GeneMANIA, STRING, SMPDB, cBioPortal, UALCAN, and TISDB databases and also 33 cancer and normal tissues in TCGA downloaded from the Genome Data Commons (GDC) data portal. Data and statistical analysis were performed using R software v4.0.3. Our results found that there were differences in the mRNA expression levels of HIF1 alpha in human pan-cancer and its corresponding normal tissues. The expression level of HIF1 alpha correlated with tumor stage in LIHC and also significantly correlated with prognosis in LIHC, LUSC, STAD, OV, PAAD, PRAD, THCA, LUAD, MESO, and READ. The small molecule pathways involved in HIF1 alpha include succinate signaling, fumarate, and succinate carcinogenesis-related pathways. The highest mutation frequency of the HIF1 alpha gene in pan-cancer was head and neck cancer, and the HIF1 alpha methylation level in most tumors is significantly reduced. HIF1 alpha was not only associated with immune cell infiltration but also with immune checkpoint genes and immune regulators TMB and MSI. There were currently 5 small molecule drugs targeting HIF1 alpha.

Automated summary

HIF1 alpha plays an important role in pan-cancer, with its expression levels correlating with tumor stage and prognosis. It is involved in multiple small molecule pathways. Head and neck cancer has the highest mutation frequency of the HIF1 alpha gene, and HIF1 alpha methylation level is reduced in most tumors. HIF1 alpha is not only associated with immune cell infiltration but also with immune checkpoint genes and tumor mutation burden.