Suvanasuthi Rooge, Therasakvichya Suwanit, Kanchanapiboon Potjanee, Promptmas Chamras, Chimnaronk Sarin
Department of Biomedical Engineering, Faculty of Engineering, Mahidol University, Nakhon Pathom, 73170, Thailand.
Faculty of Science, Chulabhorn Royal Academy, Bangkok, 10210, Thailand.
Sci Rep. 2025 Jan 2;15(1):142. doi: 10.1038/s41598-024-84080-1.
The incidence rate of cervical cancer (CC) is three times greater in Southeast Asia (SEA), where screening tests are less common than in Northern America, underlining a need for convenient self-diagnostic methods. The expression pattern of microRNAs (miRNAs) has been considered a molecular tool for non-invasive cancer diagnosis and prognosis. This study aimed at the development of the first miRNA biomarker panel for early detection of CC in Thai women. Genome-wide miRNA expression profiling was performed on cervical tissue and discharge samples from high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS) subjects. Machine learning was used for handling imbalanced data and feature selection before differential expression analysis to identify significantly dysregulated miRNA panels. Pathway analysis was conducted to provide the cellular functions involved in CC progression. The study identified a shared 18-miRNA panel for both tissue and discharge, with which the prediction model distinguished HSIL and AIS from normal samples with an accuracy of 90.9%. Three dysregulated miRNAs comprised of miR-125b-1-3p, miR-487b-3p, and miR-1180-3p in CC were first described. Most of the miRNAs in the panel were down-regulated, whereas merely miR-142-3p was significantly up-regulated in HSIL and AIS, suggesting a convenient biomarker for detecting precancerous conditions. Moreover, our miRNA panel highlighted important roles played by the cell-cell interaction pathways in CC. Together, our miRNA panel hold promise as a biomarker for the early detection of cervical cancer with cervical discharge, offering the possibility for developing non-invasive diagnostic tools.
东南亚地区宫颈癌(CC)的发病率是北美地区的三倍,在东南亚,筛查测试不如北美地区普遍,这凸显了对便捷的自我诊断方法的需求。微小RNA(miRNA)的表达模式已被视为一种用于非侵入性癌症诊断和预后评估的分子工具。本研究旨在开发首个用于早期检测泰国女性宫颈癌的miRNA生物标志物组合。对高级别鳞状上皮内病变(HSIL)和原位腺癌(AIS)患者的宫颈组织及分泌物样本进行了全基因组miRNA表达谱分析。在差异表达分析之前,使用机器学习处理不平衡数据并进行特征选择,以识别显著失调的miRNA组合。进行了通路分析以提供与宫颈癌进展相关的细胞功能。该研究确定了一个组织和分泌物样本共享的18-miRNA组合,利用该组合构建的预测模型区分HSIL和AIS与正常样本的准确率为90.9%。首次描述了在宫颈癌中失调的三个miRNA,即miR-125b-1-3p、miR-487b-3p和miR-1180-3p。该组合中的大多数miRNA表达下调,而仅miR-142-3p在HSIL和AIS中显著上调,提示其可能是检测癌前病变的便捷生物标志物。此外,我们的miRNA组合突出了细胞间相互作用通路在宫颈癌中的重要作用。总之,我们的miRNA组合有望成为通过宫颈分泌物早期检测宫颈癌的生物标志物,为开发非侵入性诊断工具提供了可能。