microRNA 比率作为粘液性交界性肿瘤和恶性卵巢肿瘤有前景的诊断生物标志物的协同作用。
Synergy of the microRNA Ratio as a Promising Diagnosis Biomarker for Mucinous Borderline and Malignant Ovarian Tumors.
发表日期:2023 Nov 06
作者:
Enora Dolivet, Léopold Gaichies, Corinne Jeanne, Céline Bazille, Mélanie Briand, Mégane Vernon, Florence Giffard, Frédéric Leprêtre, Laurent Poulain, Christophe Denoyelle, Nicolas Vigneron, Raffaèle Fauvet
来源:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
摘要:
上皮性卵巢癌 (EOC) 是一组异质性恶性肿瘤,每种都有自己的发育起源、临床行为和分子特征。粘液性卵巢癌占 EOC 病例的比例不到 5%,是一种罕见的癌症形式,预后较差,晚期 (III/IV) 期的 5 年生存率为 11%。在早期阶段,由于粘液性肿瘤体积大且异质性,这些恶性形式在临床上很难与预后较好的交界性(15%)和良性(80%)区别。因此,改善其诊断是一项挑战,因为存在恶性形式治疗不足或不必要地进行根治性手术切除的风险。 microRNA (miRNA) 在肿瘤进展中的参与及其作为诊断生物标志物的潜力越来越受到人们的认可。在本研究中,比较恶性和交界性肿瘤 FFPE 样本之间的 miRNA 微阵列表达谱,鉴定出 10 个下调和 5 个上调的恶性 miRNA,并通过单独的 RT-qPCR 进行了验证。为了克服标准化问题并提高结果的准确性,我们进行了配对上调和下调 miRNA 的比率分析。尽管 21/50 miRNA 表达比率在恶性和交界性肿瘤样本之间存在显着差异,但任何比率都可以完美地区分两组。然而,14 对 miRNA 比率(双倍比率)的组合显示出很高的区分潜力,在区分恶性和交界性卵巢肿瘤方面具有 100% 的准确度,这表明 miRNA 作为诊断工具可能具有重要的临床潜力。总之,这些基于 miRNA 的比例特征可能有助于提高组织学诊断的准确性,可能提供术前诊断以适应手术程序。
Epithelial ovarian cancers (EOCs) are a heterogeneous collection of malignancies, each with their own developmental origin, clinical behavior and molecular profile. With less than 5% of EOC cases, mucinous ovarian carcinoma is a rare form with a poor prognosis and a 5-year survival of 11% for advanced stages (III/IV). At the early stages, these malignant forms are clinically difficult to distinguish from borderline (15%) and benign (80%) forms with a better prognosis due to the large size and heterogeneity of mucinous tumors. Improving their diagnosis is therefore a challenge with regard to the risk of under-treating a malignant form or of unnecessarily undertaking radical surgical excision. The involvement of microRNAs (miRNAs) in tumor progression and their potential as biomarkers of diagnosis are becoming increasingly recognized. In this study, the comparison of miRNA microarray expression profiles between malignant and borderline tumor FFPE samples identified 10 down-regulated and 5 up-regulated malignant miRNAs, which were validated by individual RT-qPCR. To overcome normalization issues and to improve the accuracy of the results, a ratio analysis combining paired up-regulated and down-regulated miRNAs was performed. Although 21/50 miRNA expression ratios were significantly different between malignant and borderline tumor samples, any ratio could perfectly discriminate the two groups. However, a combination of 14 pairs of miRNA ratios (double ratio) showed high discriminatory potential, with 100% of accuracy in distinguishing malignant and borderline ovarian tumors, which suggests that miRNAs may hold significant clinical potential as a diagnostic tool. In summary, these ratio miRNA-based signatures may help to improve the precision of histological diagnosis, likely to provide a preoperative diagnosis in order to adapt surgical procedures.