Pan-Cancer Analysis of ARHGAP35 Reveals Prognostic Relevance in Breast and Cervical Cancers.

Rho GTPase-activating protein ARHGAP35 has been linked to tumour progression, but its pan-cancer activity is not well understood. The current study has explored gene expression, mutation patterns and clinical relevance of ARHGAP35 in several cancers, using TCGA datasets. Analysis of expression showed that TGCT, KIRP and UCEC were significantly down regulated and BRCA, ESCA, KICH and LAML were highly expressed. Oncoprint findings revealed that genomic changes on ARHGAP35 are not common, with less than 2 percent of cases reported, and that amplification and truncating mutations are the most common. Mutation distribution analysis was used to show that there was a dispersed pattern with no hotspots but moderate clustering was found in the middle of the protein. Functional domain mapping implied that a relatively smaller number of mutations in conserved areas would occur, but variants in the RhoGAP domain can have an effect on tumour-associated signalling. Genetic modification of ARHGAP35 showed survival analysis results in worse prognosis of breast and cervical cancers, with decreased median survival rates of altered groups. Comprehensively, the results indicate that ARHGAP35 can act more as a tumour suppressor, and that loss-of-function mutations may occur in some cases, which lead to cancer development. Overall, these results indicate the potential of ARHGAP35 as a prognostic biomarker and offer preliminary clues to its potential role in cancer biology.