长链非编码RNA PVT1、CCAT2和TCF7L2以及miR-33和c-Myc在口腔鳞状细胞癌和口腔扁平苔藓患者中的表达。

Long non-coding RNAs PVT1, CCAT2, and TCF7L2, and miR-33 and c-Myc expression in oral squamous cell carcinoma and oral lichen planus patients.

作者信息

Gholizadeh Narges, Yousefian Marzieh, Mohammadpour Hadiseh, Razavi Amirnader Emami, Talaei Sanam, Sheykhbahaei Nafiseh

机构信息

Department of Oral & Maxillofacial Medicine, School of Dentistry, Tehran University of Medical Science, Tehran, Iran; Department of Oral & Maxillofacial Surgery, School of Dentistry, Tehran University of Medical Science, Tehran, Iran.

Department of Oral & Maxillofacial Medicine, School of Dentistry, Tehran University of Medical Science, Tehran, Iran.

出版信息

J Craniomaxillofac Surg. 2025 Aug;53(8):1197-1204. doi: 10.1016/j.jcms.2025.04.006. Epub 2025 May 12.

DOI:10.1016/j.jcms.2025.04.006

PMID:40360347

Abstract

OBJECTIVE

The objective of this study was to assess the potential of TCF7L2, CCAT2, and PVT1 LncRNAs, c-Myc, and miR-33 as biomarkers for early diagnosis and differentiation of oral squamous cell carcinoma (OSCC) and premalignant lesions.

DESIGN

Bioinformatics tools, including COSMIC, GeneMANIA, PathVisio, KEGG Pathway Database, IntOGen, and WikiPathways, were used to investigate the signaling pathways of cancer-associated genes. The limma package was utilized for statistical analysis to identify Differentially Expressed Genes (DEGs) between OSCC tumor and normal samples. The regulatory microRNAs were analyzed using miRDB, miRWalk, and TargetScan. The type of cancer for analysis was selected using IntOGen. The expression levels of LncRNAs, miR-33, and c-Myc were measured by polymerase chain reaction (PCR) in 28 OLP and 30 OSCC tissue samples, compared to 30 healthy and 30 OSCC-adjacent tissue specimens as control groups. Data were analyzed using the Mann-Whitney test, receiver operating characteristic (ROC) curve, and multiple linear regression.

RESULTS

The expression of c-Myc (3.53 ± 2.78 vs 0.93 ± 0.50), PVT1 (10.94 ± 8.49 vs 0.91 ± 0.48), CCAT2 (11.77 ± 10.00 vs 0.92 ± 0.95), and TCF7L2 (6.48 ± 4.30 vs 1.27 ± 0.96) was significantly higher in OSCC samples compared to OLP (P < 0.001). Conversely, miR-33 expression was significantly lower in OSCC samples (0.24 ± 0.25 vs 4.90 ± 3.90). There was a significant correlation between c-Myc, CCAT2, PVT1, and miR-33 expression and clinicopathological characteristics of OSCC specimens. In OSCC samples, c-Myc, PVT1, CCAT2, and TCF7L2 showed a significant positive correlation with each other, while miR-33 expression was negatively correlated with the overexpression of other genes. The area under the curve (AUC) for c-Myc, PVT-1, CCAT2, miR-33, and TCF7L2 were 0.917, 1.000, 0.979, 0.006, and 0.929, respectively.

CONCLUSIONS

Our findings suggest that c-Myc and LncRNAs (TCF7L2, PVT1, and CCAT2) are upregulated and miR-33 is downregulated in OSCC compared to OLP samples. These genes may serve as potential genetic biomarkers for diagnosis and prediction of clinicopathological features of OSCC.

摘要

目的

本研究的目的是评估TCF7L2、CCAT2和PVT1长链非编码RNA（LncRNAs）、c-Myc和miR-33作为口腔鳞状细胞癌（OSCC）及癌前病变早期诊断和鉴别生物标志物的潜力。

设计

使用包括COSMIC、GeneMANIA、PathVisio、KEGG通路数据库、IntOGen和WikiPathways在内的生物信息学工具来研究癌症相关基因的信号通路。利用limma软件包进行统计分析，以鉴定OSCC肿瘤样本与正常样本之间的差异表达基因（DEGs）。使用miRDB、miRWalk和TargetScan分析调控性微小RNA。使用IntOGen选择用于分析的癌症类型。通过聚合酶链反应（PCR）测量28例口腔扁平苔藓（OLP）和30例OSCC组织样本中LncRNAs、miR-33和c-Myc的表达水平，并与30例健康组织样本和30例OSCC旁组织标本作为对照组进行比较。使用曼-惠特尼检验、受试者工作特征（ROC）曲线和多元线性回归分析数据。

结果

与OLP相比，OSCC样本中c-Myc（3.53±2.78 vs 0.93±0.50）、PVT1（10.94±8.49 vs 0.91±0.48）、CCAT2（11.77±10.00 vs 0.92±0.95）和TCF7L2（6.48±4.30 vs 1.27±0.96）的表达显著更高（P<0.001）。相反，OSCC样本中miR-33的表达显著更低（0.24±0.25 vs 4.90±3.90）。c-Myc、CCAT2、PVT1和miR-33的表达与OSCC标本的临床病理特征之间存在显著相关性。在OSCC样本中，c-Myc、PVT1、CCAT2和TCF7L2彼此之间呈显著正相关，而miR-33的表达与其他基因的过表达呈负相关。c-Myc、PVT-1、CCAT2、miR-33和TCF7L2的曲线下面积（AUC）分别为0.917、1.000、0.979、0.006和0.929。