Exosomal C5orf46 gene: Pan-cancer Analysis of its Implication in Cancer Prognosis Risk Indication and Tumor Microenvironment Remodeling

Abstract

Abstract Background Exosomes have been important particles that mediate cellular communication, and more importantly, they have been gradually known to participate in multiple critical processes of cancer development including angiogenesis, immune invasion, cancer metastasis, and drug resistance. However, as an exosomal gene, the functions of C5orf46 in cancers are still lack of understanding. In the study, the gene’s role in the formation and development of different tumor processes would be investigated comprehensively for potential further clinical application. Methods The study started with the genetic characteristics and physicochemical properties analysis of C5orf46 gene, and then the gene expression as well as alteration patterns in broad spectrum human cancers were analyzed. Further, the potential post transcription modulations of the gene was investigated, followed by survival analysis including both overall survival and recurrence free survival in pan-cancer. Moreover, the correlation between C5orf46 gene and multiple critical cancer parameters including angiogenesis, cancer stemness, DNA repair, and immune infiltration were in succession explored. Results Firstly, basic physicochemical properties of C5orf46 were preliminary computed including its aminoacid composition, estimated molecular weight and protein half life. Then, based on the gene expression as well as survival analysis result, we noticed that C5orf46 was aberrant up-regulated in various types of human cancers which was partly due to decreased DNA methylation level in cancers, and of clinical significance, the changed expression of the gene correlated directly with worse patients survival. Moreover, C5orf46 gene was indicated to be associated with multiple critical cancer traits including microenvironment angiogenesis, immune infiltration, extra cellular matrix (ECM) degradation and epithelial-mesenchymal transition (EMT). Further, C5orf46 gene was indicated to correlate with the sensitivity of several chemotherapy related drugs. Conclusions Based on TCGA pan-cancer data and series of analysis, we discovered that exosome containing C5orf46 potentially works as an oncogene, which was highly expressed in multiple cancers and correlated with worse patients survival. Besides, C5orf46 gene was associated with multiple cancers clinical traits. Although more detailed experiments and clinical trials are needed to validate the gene function in each independent type of cancer, the study shall reveal valuable strategies concerning the role of C5orf46 in pan-cancer and its potential as a novel therapeutic target.