22P - Comparative analysis of miRNA biomarkers in liquid-based cytology and plasma for early detection of high-grade cervical intraepithelial neoplasia

Background

The miRNA expression analysis has shown promise as molecular biomarkers for early cervical cancer (CC) detection in liquid biopsy, and previous studies often focused on a single biofluid, such as liquid-based cytology (LBC) or blood (serum/plasma). However, comparing different biofluids is crucial to identify consistent biomarkers across sample types, enhancing the reliability and accuracy of miRNA-based diagnosis. In this study, we aimed to identify a common miRNA signature in LBC and plasma of patients with high-grade cervical intraepithelial neoplasia (CIN), and their interaction with molecular pathways related to CC in a prospective study.

Methods

We analyzed the same casuistry (n = 70) for both LBC and plasma samples. The participants were divided into two groups: a case group consisting of women diagnosed with CIN 2/3 (n = 35) and a control group of women without cervical precursor lesions (n = 35). miRNA expression profiling involved the nCounter® miRNA Expression Assay (NanoString Technology), evaluating 800 targets. Functional and enrichment analyses were performed using mirDIP and Cytoscape (Reactome plugin), respectively.

Results

We identified 57 miRNAs in LBC and 33 miRNAs in plasma samples that were differentially expressed between case and control groups (p ≤ 0.05). Four miRNAs exhibited differential expression in both biofluids (fold change > 1.15 and p ≤ 0.05). In a multivariate logistic regression model combining these miRNAs with alcoholism and smoking, only the underexpression of miR-339-3p (LBC: OR = 7.71, 95% CI = 1.73 – 45.0, p = 0.012; plasma: OR = 9.67, 95% CI = 2.01 - 67.6, p = 0.010) significantly predicted CIN 2/3. miR-339-3p had AUC values of 0.67 and 0.64 in LBC and plasma samples, respectively. Additionally, we identified 193 target genes for miR-339-3p, mainly related with pathways in cancer, apoptosis, direct p53 effectors, and Polymerase III transcription.

Conclusions

This study highlights miR-339-3p potential as a promising molecular biomarker for early CIN 2/3 detection in both LBC and plasma samples. Furthermore, consistent expression across biofluids enhances reliability, suggesting its utility in improving the accuracy of miRNA-based CC diagnosis.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

National Oncology Care Support Program (Pronon) (Pronon) and Barretos Cancer Hospital.

Disclosure

All authors have declared no conflicts of interest.