The multifaceted role of the potassium channel KCNK1 in the early detection and prognostication of high-grade serous cancer
Subarnarekha Chatterji, Elaine Craig, Kathryn Egerton, Paula Haddock, James Beirne, Laura Feeney, W Glenn McCluggage, Sam Leung, C Blake Gilks, Sarah J Storr, Stewart G Martin, Karen D McCloskey, Stephen McQuaid, Paul Mullan, Niamh E Buckley
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Source: Crossref
Published: Sep 23, 2026
DOI: 10.1186/s13048-026-02281-w
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Abstract Background The sixth most common cancer in females in the UK, ovarian cancer remains a significant health burden due to its aggressive nature and stagnant mortality trends. The current gold standard biomarker, CA-125, has notable limitations, including low sensitivity in early-stage disease and elevation in benign conditions. This underscores the urgency for a deeper molecular understanding of the disease and the need to develop biomarkers for early diagnosis, patient stratification, and tailored treatments. Methylation status, gene and immunohistochemical protein expression of the potassium ion channel, KCNK1, were assessed between normal fallopian tube, serous tubal intraepithelial carcinoma, and high-grade serous cancer. Results KCNK1 mRNA expression was significantly higher in cancer than in normal fallopian tube, and higher expression in Type I and lower grade ovarian cancer predicted significantly improved outcome in 3 independent cohorts. Within high-grade serous cancer, high KCNK1 immunohistochemical expression independently predicted improved outcome. As a diagnostic marker, KCNK1 mRNA was elevated in high-grade serous cancer against normal fallopian tube, albeit with low specificity and sensitivity. However, KCNK1 DNA methylation levels showed strong diagnostic capability with 98% sensitivity and specificity, significantly outperforming CA-125 in specificity. Conclusion This study highlights the potential of KCNK1 as a novel prognostic and diagnostic biomarker for high-grade serous cancer. The methylation biomarker shows potential for early disease detection and possible utility in minimally invasive blood-based diagnostic assays. Furthermore, KCNK1 may help identify patients unlikely to benefit from standard care, guiding alternative treatment strategies for optimal clinical outcomes.
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