基于元特征的微小RNA候选物作为口腔癌潜在生物标志物的研究

Meta-signature guided investigation of miRNA candidates as potential biomarkers of oral cancer.

作者信息

Stojkovic Goran, Jovanovic Ivan, Dimitrijevic Milovan, Jovanovic Jasmina, Tomanovic Nada, Stankovic Aleksandra, Arsovic Nenad, Boricic Ivan, Zeljic Katarina

机构信息

Clinic for Otorhinolaryngology and Maxillofacial Surgery, University Clinical Center Serbia, Belgrade, Serbia.

Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

出版信息

Oral Dis. 2023 May;29(4):1550-1564. doi: 10.1111/odi.14185. Epub 2022 Mar 16.

DOI:10.1111/odi.14185

PMID:35262985

Abstract

OBJECTIVES

This study aimed to experimentally validate dysregulated expression of miRNA candidates selected through updated meta-analysis of most commonly deregulated miRNAs in oral cancer and to explore their diagnostic and prognostic potential.

MATERIALS AND METHODS

Five miRNAs (miR-31-3p, miR-135b-5p, miR-18a-5p, miR-30a-5p and miR-139-5p) from updated meta-signature were selected for validation by qRT-PCR method in 35 oral cancer clinical specimens and adjacent non-cancerous tissue.

RESULTS

Updated meta-analysis has identified 13 most commonly deregulated miRNAs in oral cancer. Seven miRNAs were consistently up-regulated (miR-21-5p, miR-31-3p, miR-135b-5p, miR-31-5p, miR-424-5p, miR-18a-5p and miR-21-3p), while five were down-regulated (miR-139-5p, miR-30a-3p, miR-375-3p, miR-376c-3p and miR-30a-5p). Increased expression of miR-31-3p and miR-135b-5p, and decreased expression of miR-139-5p and miR-30a-5p were confirmed in oral cancer compared to adjacent non-cancerous tissue. A three miRNAs combination (miR-31-3p, miR-139-5p and miR-30a-5p) gave the most promising diagnostic potential for discriminating oral cancer from non-cancerous tissue (AUC: 0.780 [95% CI: 0.673-0.886], p < 0.0005, sensitivity 94.3%, specificity 51.4%). High expression of miR-135b-5p, miR-18a-5p and miR-30a-5p was associated with poor survival (p = 0.003, p = 0.048, p = 0.016 respectively).

CONCLUSION

miR-31-3p, miR-139-5p and miR-30a-5p panel was confirmed as a potential diagnostic biomarker when distinguishing oral cancer from non-cancerous tissue. miR-135b-5p, miR-18a-5p and miR-30a-5p might serve as potential biomarkers of poor survival of oral cancer patients.

摘要

目的

本研究旨在通过实验验证通过对口腔癌中最常见的失调微小RNA进行更新的荟萃分析所选择的微小RNA候选物的失调表达，并探索它们的诊断和预后潜力。

材料与方法

从更新的元特征中选择5种微小RNA（miR-31-3p、miR-135b-5p、miR-18a-5p、miR-30a-5p和miR-139-5p），通过qRT-PCR方法在35例口腔癌临床标本和相邻的非癌组织中进行验证。

结果

更新的荟萃分析确定了口腔癌中13种最常见的失调微小RNA。7种微小RNA持续上调（miR-21-5p、miR-31-3p、miR-135b-5p、miR-31-5p、miR-424-5p、miR-18a-5p和miR-21-3p），而5种下调（miR-139-5p、miR-30a-3p、miR-375-3p、miR-376c-3p和miR-30a-5p）。与相邻的非癌组织相比，口腔癌中miR-31-3p和miR-135b-5p表达增加，miR-139-5p和miR-30a-5p表达降低。三种微小RNA组合（miR-31-3p、miR-139-5p和miR-30a-5p）在区分口腔癌和非癌组织方面具有最有前景的诊断潜力（AUC：0.780[95%CI：0.673-0.886]，p<0.0005，敏感性94.3%，特异性51.4%）。miR-135b-5p、miR-18a-5p和miR-30a-5p的高表达与较差的生存率相关（分别为p=0.003、p=0.048、p=0.016）。