A three miRNAs signature for predicting the transformation of oral leukoplakia to oral squamous cell carcinoma

Huan Chen; Xiangzhen Liu; Zhenning Jin; Chenyu Gou; Minglu Liang; Li Cui; Xinyuan Zhao

A three miRNAs signature for predicting the transformation of oral leukoplakia to oral squamous cell carcinoma

Am J Cancer Res. 2018 Aug 1;8(8):1403-1413. eCollection 2018.

Authors

Huan Chen¹, Xiangzhen Liu², Zhenning Jin³, Chenyu Gou⁴, Minglu Liang⁵, Li Cui³, Xinyuan Zhao⁵

Affiliations

¹ Shenzhen Stomatological Hospital, Southern Medical University Shenzhen 518000, China.
² Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-sen University Guangzhou 510080, China.
³ UCLA School of Dentistry Los Angeles, CA 90095, USA.
⁴ Sixth Affiliated Hospital, Sun Yat-sen University Guangzhou 510655, China.
⁵ Stomatological Hospital, Southern Medical University Guangzhou 510260, China.

PMID: 30210912
PMCID: PMC6129488

Abstract

Oral squamous cell carcinoma (OSCC) remains to be a global health problem. However, the underlying molecular mechanisms regulating the oral leukoplakia (OLK) to OSCC remain poorly known. MicroRNAs (miRNAs) expression profiles of GSE33299 and GSE62809 were downloaded from gene expression omnibus (GEO) respectively. R software and bioconductor packages were used to compare and identify the differentially expressed miRNAs between OLK tissues and OLK transformed OSCC (OLK-OSCC). The target genes of commonly changed miRNAs were then subjected to gene ontology (GO) enrichment analysis, pathway analysis and miRNA-target genes network analysis. The prediction power of commonly changed miRNAs was further tested in an independent cohort. In total, 161 (88 upregulated and 73 downregulated) and 68 (19 upregulated and 49 downregulated) markedly altered miRNAs were identified from GSE33299 and GSE62809 respectively. The downstream targets of these differentially expression miRNAs in the two cohorts shared many top enriched GO and KEGG pathways. A set of three miRNAs signature including miR-129-5p, miR-296-5p and miR-450b-5p was commonly changed in both GSE33299 and GSE62809. Functional analysis revealed that the downstream target genes of the miRNA signature were associates with transcriptional regulation, estrogen signaling pathway, p53 signaling pathway and RIG-I-like receptor signaling pathway. This three-gene signature was further successfully validated in another independent cohort. The expression levels of miR-129-5p and miR-296-5p were significantly downregulated in OLK-OSCC tissues compared to OLK tissues, while miR-450b-5p levels were higher in OLK-OSCC tissues. In addition, this three miRNAs signature could discriminate OLK from OLK-OSCC with high accuracy. In conclusion, our study has identified a three miRNAs signature that might help predict the transformation of OLK to OSCC. Which will provide useful guidance for therapeutic applications.

Keywords: Functional analysis; MicroRNAs; oral leukoplakia; oral squamous cell carcinoma.