Exploring shared microRNA profiles in liquid-based cytology and plasma as biomarkers of high-grade intraepithelial lesions

High-grade cervical intraepithelial lesions (CIN 2/3) are critical targets for early detection in cervical cancer prevention. MicroRNAs are stable, tissue-specific molecules involved in cancer-related pathways and can be detected in minimally invasive samples, making them suitable for use in the context of liquid biopsies. This exploratory study aimed to identify differentially expressed microRNAs in paired liquid-based cytology (LBC) and plasma samples from women with CIN 2/3, and to evaluate miR-339-3p as a potential biomarker. Samples from 70 women (35 cases with histologically confirmed high-grade lesions and 35 age-matched controls with normal cytology and negative HPV tests) were analyzed using a commercial microRNA panel on the NanoString platform. We identified 57 dysregulated microRNAs in LBC samples and 33 in plasma, with four shared between both matrix types. Among these, miR-339-3p was the only one consistently upregulated and significantly associated with case status. In LBC samples, the area under the curve was 0.65; in plasma, 0.64. Pathway analysis suggested its involvement in apoptosis-related pathways, including PI3K-Akt and p53. Moreover, this study highlights the value of integrating microRNA profiling across local and systemic samples to advance biomarker discovery in cervical cancer.