C5orf46: a promising prognosis risk indicator with implication in the remodeling of KIRC and pan-cancer tumor microenvironments.

Introduction: C5orf46 is a recently discovered tumor-progression-related gene whose function in most cancers is still unknown, especially its potential role in regulating the tumor microenvironment (TME). The aim of the study is to explore the function of the C5orf46 gene in human pan-cancer, including kidney renal clear cell carcinoma (KIRC), for potential clinical application. Methods: The study started with the physicochemical properties of C5orf46, then the gene expression as well as alteration patterns in diverse cancers, followed by its post-transcription modulation, and then survival analysis. Moreover, the correlations between C5orf46 and multiple cancer TME-related parameters, including angiogenesis, extracellular matrix (ECM) degradation, and immune infiltration, were explored sequentially. Furthermore, C5orf46's association with other critical cancer features, for instance, cancer stemness, tumor epithelial-mesenchymal transition (EMT), and DNA repair, was also investigated. Results: Firstly, the physicochemical properties, including amino acid composition, estimated molecular weight, and protein half-life, of the C5orf46 gene were computed sequentially. Then, based on gene expression as well as survival analysis results, C5orf46 was shown to be upregulated in various human cancers, wherein KIRC showed the greatest difference in C5orf46 expression between cancer and corresponding normal tissues. The change in expression was partly due to DNA methylation modulation. Meanwhile, of greater clinical significance, the upregulated 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, was validated. Furthermore, the C5orf46 gene was indicated to correlate with the sensitivity of several chemotherapy-related drugs. Conclusions: Based on TCGA pan-cancer data and validation of local hospital samples, C5orf46 was indicated to potentially work as an oncogene in diverse cancers, and the gene was associated with multiple critical cancer traits.