Dataset Information

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

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.

SUBMITTER: Chen H

PROVIDER: S-EPMC6129488 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Chen Huan H Liu Xiangzhen X Jin Zhenning Z Gou Chenyu C Liang Minglu M Cui Li L Zhao Xinyuan X

American journal of cancer research 20180801 8

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 ...[more]

PMID: 30210912

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Project description:BackgroundOral squamous cell carcinoma (OSCC) is one of the most common forms of cancer associated with the presence of precancerous oral leukoplakia. Given the poor prognosis associated with oral leukoplakia, and the difficulties in distinguishing it from cancer lesions, there is an urgent need to elucidate the molecular determinants and critical signal pathways underlying the malignant transformation of precancerous to cancerous tissue, and thus to identify novel diagnostic and therapeutic target.ResultsWe have utilized two dimensional electrophoresis (2-DE) followed by ESI-Q-TOF-LC-MS/MS to identify proteins differentially expressed in six pairs of oral leukoplakia tissues with dysplasia and oral squamous cancer tissues, each pair was collected from a single patient. Approximately 85 differentially and constantly expressed proteins (> two-fold change, P < 0.05) were identified, including 52 up-regulated and 33 down-regulated. Gene ontological methods were employed to identify the biological processes that were over-represented in this carcinogenic stage. Biological networks were also constructed to reveal the potential links between those protein candidates. Among them, three homologs of proteosome activator PA28 a, b and g were shown to have up-regulated mRNA levels in OSCC cells relative to oral keratinocytes.ConclusionVarying levels of differentially expressed proteins were possibly involved in the malignant transformation of oral leukoplakia. Their expression levels, bioprocess, and interaction networks were analyzed using a bioinformatics approach. This study shows that the three homologs of PA28 may play an important role in malignant transformation and is an example of a systematic biology study, in which functional proteomics were constructed to help to elucidate mechanistic aspects and potential involvement of proteins. Our results provide new insights into the pathogenesis of oral cancer. These differentially expressed proteins may have utility as useful candidate markers of OSCC.

Project description:BackgroundAutophagy, a highly conserved self-digesting process, has been deeply involved in the development and progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of autophagy-related genes (ARGs) for OSCC still remains unclear. Our study set out to develop a multigene expression signature based on ARGs for individualized prognosis assessment in OSCC patients.MethodsBased on The Cancer Genome Atlas (TCGA) database, we identified prognosis-related ARGs through univariate COX regression analysis. Then we performed the least absolute shrinkage and selection operator (LASSO) regression analysis to identify an optimal autophagy-related multigene signature with the subsequent validation in testing set, GSE41613 and GSE42743 datasets.ResultsWe identified 36 prognosis-related ARGs for OSCC. Subsequently, the multigene signature based on 13 prognostic ARGs was constructed and successfully divided OSCC patients into low and high-risk groups with significantly different overall survival in TCGA training set (p < 0.0001). The autophagy signature remained as an independent prognostic factor for OSCC in univariate and multivariate Cox regression analyses. The area under the curve (AUC) values of the receiver operating characteristic (ROC) curves for 1, 3, and 5-year survival were 0.758, 0.810, 0.798, respectively. Then the gene signature was validated in TCGA testing set, GSE41613 and GSE42743 datasets. Moreover, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and single-sample gene set enrichment analysis (ssGSEA) revealed the underlying biological characteristics and signaling pathways associated with this signature in OSCC. Finally, we constructed a nomogram by combining the gene signature with multiple clinical parameters (age, gender, TNM-stage, tobacco, and alcohol history). The concordance index (C-index) and calibration plots demonstrated favorable predictive performance of our nomogram.ConclusionIn summary, we identified and verified a 13-ARGs prognostic signature and nomogram, which provide individualized prognosis evaluation and show insight for potential therapeutic targets for OSCC.

Dataset Information

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

Publications

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

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