TWIK Complex Expression in Prostate Cancer: Insights into the Biological and Therapeutic Significances of Potassium Ion Channels in Clinical Cancer

Ion channels play ubiquitous roles in the maintenance of tumour cell homeostasis and hence are attractive targets in the molecular pathogenesis and progression of prostate cancer (PCa). This study aimed to investigate the roles of the potassium ion channel complex TWIK, a member of the two-pore-domain potassium channel subfamily, in clinical PCa. The clinicopathological, gene expression, and copy number data of three clinical PCa cohorts from cancer genomics databases were analysed to determine the clinicopathological, biological, and therapeutic significances of the TWIK expression signature using statistical correlations and gene enrichment techniques. The results show that the PCa subset with high TWIK expression exhibited associations with worse pathological tumours, nodes, and overall tumour stages, as well as with high Gleason scores, high prognostic grade groups, and poorer responses to androgen deprivation therapy. Furthermore, a combination of gene set and gene ontology enrichment analyses showed that the PCa subset with high TWIK complex expression was differentially enriched for known oncogenic signalling pathways, aberrant ubiquitination and glucuronidation activities, and for gene sets of ion channel blockers and chemotherapeutic agents. The implications of these findings with respect to cancer progression, therapeutic response, and opportunities for therapeutic targeting of the TWIK complex are discussed, along with the potential of the TWIK complex as a predictive biomarker for integrated, multitargeted therapy.