Exploring the diversified roles of Anoctamin Family in Pan-Cancer

Abstract

Abstract Background Anoctamin family (Transmembrane Protein 16), has gained growing attention for generating exosome and ectosome to mediate cancer cell communication in the process of phospholipid scrambling. However, former studies only focused on one narrow process in a single cancer. Instead, we designed a multidimensional study to comprehensively investigate the impact of ANO family on eight critical multi-omics cancer features in TCGA pan-cancer cohort. Methods TCGA pan-cancer cohorts were downloaded from UCSC xena. Differential analysis, survival analysis, and correlation analysis with tumor mutation burden, immune-phenotyping, stemness, cell proportion of tumor microenvironment, and drug sensitivity were conducted by R software. Alteration landscape was obtained from cBioportal with STRING database showing the protein-protein interaction network. Nanoparticle Tracking Analysis and Western Blot were employed to identify the ANO5 exosome. Results Extensive and profound associations were found between ANO family and eight crucial cancer features, including clinical prognosis, metastasis, drug resistance, tumor mutation burden, stemness, and tumor microenvironment. ANO1 possessed a high mutation frequency and is a driver gene in multiple cancers. ANO5 can exist in exosome to mediate cell-cell communication. Conclusions ANO family broadly participates in the proliferation, metastasis, and drug resistance in a barrage of cancers by generating extracellular vesicles to mediate cell-cell communication and interacting with TMB, stemness, stromal and immune cell proportions in tumor microenvironment. ANO members can serve as reliable biomarkers for prognosis of cancer, as well as promising targets for trans-cancer treatment.