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

## TL;DR

This study explores how the TWIK potassium channel complex contributes to prostate cancer growth and drug response in real patients, offering new therapeutic insights.

## Contribution

The study identifies TWIK complex expression as a potential biomarker and therapeutic target in clinical prostate cancer.

## Key findings

- High TWIK complex expression is associated with worse prostate cancer outcomes and poor response to androgen deprivation therapy.
- TWIK expression correlates with oncogenic pathways and may predict response to chemotherapy and ion channel blockers.
- The TWIK complex is a potential therapeutic target for multitargeted prostate cancer treatment.

## Abstract

The death rate from prostate cancer worldwide is still high; hence, there is a need to investigate the biological mechanisms of the disease in order to identify cancer cell vulnerabilities. This study investigates the roles of the potassium channel complex, called TWIK, in natural prostate cancer in actual patients. The rationale for studying the TWIK complex in prostate cancer is that many functions have been found for ion channels in cancer cells growing in experimental cultures, but the implications of these functions in natural cancers have not been studied in depth. This study investigates the roles of the TWIK complex in promoting prostate cancer growth. It also investigates the potential for using TWIK complex expression to predict whether prostate cancer patients would respond to certain types of anti-cancer drugs. The results show that, indeed, the TWIK complex supports the growth of cancer cells in real patients. They also show that the expression of the TWIK complex may be able to predict which anti-cancer drugs cancer patients may respond to. In addition, they reveal that cancers with high TWIK complex expression may have potential therapeutic targets.

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.