C5orf46: a Promising Prognosis Risk Indicator with Implication in the Remodeling of KIRC included Pan-cancer Tumor Microenvironment

Background C5orf46 is a recently discovered tumor progression related gene whose function in most cancers are still unknown, especially its potential regulation on tumor microenvironment (TME). The aim of the study is to explore C5orf46 gene function in kidney renal clear cell carcinoma (KIRC) included human pan-cancer for potential clinical application. Methods The study started with the physicochemical property of C5orf46, and then the gene expression as well as alteration patterns in diverse cancers, followed by post transcription modulation of the gene and then survival analysis. Moreover, the correlation between C5orf46 and multiple cancer TME related parameters including angiogenesis, extracellular matrix (ECM) degradation and immune infiltration were in succession explored. Further, C5orf46 association with others critical cancer features for instance cancer stemness, tumor epithelial mesenchymal transition (EMT) and DNA repair were also investigated. Results Firstly, physicochemical properties including the aminoacid composition, estimated molecular weight and protein half life of C5orf46 gene were in succession computed. Then, based on gene expression as well as survival analysis result, C5orf46 was shown to be up-regulated in various human cancers, of which KIRC was the top cancer with highest C5orf46 expression difference between cancer and corresponding normal tissues. And the changed expression was partly due to DNA methylation modulation. Meanwhile, of more clinical significance, the up-regulated C5orf46 expression was correlated with both worse patients overall survival and shorter recurrence free survival. Moreover, the association between C5orf46 and multiple critical cancer traits including microenvironment angiogenesis, immune infiltration, ECM degradation and cancer EMT were validated. Further, C5orf46 gene was indicated to correlate with the sensitivity of several chemotherapy related drugs. Conclusions Based on TCGA pan-cancer data and local hospital samples validation, C5orf46 was indicated to potentially works as an oncogene in diverse cancers, and the gene was associated with multiple critical cancers traits.