Scripcariu Ioana-Sadiye, Gisca Tudor, Botezatu Anca, Socolov Demetra, Vasilache Ingrid-Andrada, Diaconu Carmen, Fudulu Alina
Department of Mother and Child Care "Grigore T. Popa", University of Medicine and Pharmacy, 700115 Iasi, Romania.
Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania.
J Clin Med. 2025 May 15;14(10):3452. doi: 10.3390/jcm14103452.
: Molecular triage strategies for cervical lesions based on miR-124-2 and FAM19A4 are poorly studied in various populations. The aim of this prospective study was to evaluate the individual and combined predictive performance of these two markers for the prediction of various histological categories of cervical lesions. : An FAM19A4 and miR124-2 methylation analysis was performed on 70 samples from patients negative for intraepithelial lesion or malignancy (NILM), cervical intraepithelial neoplasia (CIN)1-3 and squamous cervical carcinoma (SCC), along with human papillomavirus (HPV) genotyping and cytological and histopathological assessment. Descriptive statistics examined clinical associations, while sensitivity analysis evaluated the predictive performance of these markers individually and combined. : The sensitivity of miR-124-2 was 28.1%, while its specificity was 86.8% for SCC. The ROC values ranged between 0.25 and 0.62 for the evaluated histological categories, suggesting a poor to moderate predictive performance. FAM19A4 had a sensitivity of 36% for predicting CIN3 and SCC, as well as a high specificity for CIN3 and SCC (88.9%), with ROC values between 0.35 and 0.73 for the evaluated histological categories. The combined tests improved the PPV for higher-risk lesions (CIN3, SCC), but did not significantly improve the ROC values. FAM19A4 achieved the best performance for the prediction of CIN2+ (ROC: 0.64) and CIN3+ lesions (ROC: 0.73). : We hypothesize that while not suitable as stand-alone diagnostic tools, such biomarkers may aid in stratifying patients and optimizing referral decisions, pending further validation in larger, population-based cohorts.
基于miR-124-2和FAM19A4的宫颈病变分子分类策略在不同人群中的研究较少。这项前瞻性研究的目的是评估这两种标志物对宫颈病变不同组织学类别的个体及联合预测性能。
对70例上皮内病变或恶性肿瘤阴性（NILM）、宫颈上皮内瘤变（CIN）1-3和宫颈鳞状细胞癌（SCC）患者的样本进行FAM19A4和miR124-2甲基化分析，同时进行人乳头瘤病毒（HPV）基因分型以及细胞学和组织病理学评估。描述性统计分析临床相关性，敏感性分析评估这些标志物的个体及联合预测性能。
miR-124-2对SCC的敏感性为28.1%，特异性为86.8%。在所评估的组织学类别中，ROC值在0.25至0.62之间，表明预测性能较差至中等。FAM19A4对CIN3和SCC的预测敏感性为36%，对CIN3和SCC具有较高的特异性（88.9%），在所评估的组织学类别中，ROC值在0.35至0.73之间。联合检测提高了高危病变（CIN3、SCC）的阳性预测值，但未显著提高ROC值。FAM19A4在预测CIN2+（ROC：0.64）和CIN3+病变（ROC：0.73）方面表现最佳。
我们推测，虽然这些生物标志物不适合作为独立的诊断工具，但在更大规模的基于人群的队列中进一步验证之前，它们可能有助于对患者进行分层并优化转诊决策。
