CLEC14A methylation marker detects HSIL and cervical cancer with 100% sensitivity and 95.3% specificity in a cohort of 431 participants.

IntroductionDespite advancements in cervical cancer early detection, such as HPV screening, their inherent limitations, such as unsatisfactory specificity, necessitate the discovery of novel, highly accurate biomarkers for cervical cancer and its precancerous high-grade squamous intraepithelial lesions (HSILs).MethodsIn this study, we identified a novel methylation marker, the cg05057720 site within the CLEC14A gene, through an initial analysis of The Cancer Genome Atlas (TCGA) and independent validation in the GSE46306 dataset. The marker’s clinical utility was further evaluated using the Quantitative Amplification of Specific Methylation (QASM) assay across a comprehensive cohort of 431 participants, including normal (n=130), LSIL (n=83), HSIL (n=195), and tumor samples (n=23).ResultsWe observed a progressive increase in CLEC14A cg05057720 methylation correlating with lesion severity, where median levels were 0% in normal samples, 2.9% in LSIL, 25.7% in HSIL, and 48.6% in tumors. In receiver-operating characteristic (ROC) analysis, the marker demonstrated exceptional diagnostic performance, achieving a sensitivity of 100% and a specificity of 95.3% for the detection of HSIL and invasive cancer in the validation cohort.DiscussionThis proof-of-concept work establishes CLEC14A cg05057720 as a sensitive and specific epigenetic biomarker, providing a robust theoretical basis for utilizing this marker to improve risk stratification and reduce unnecessary tests and treatments, though future large-scale multi-center prospective validations are warranted to further confirm these findings.