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A 3-miRNA signature predicts survival of patients with hypopharyngeal squamous cell carcinoma after post-operative radiotherapy.

ABSTRACT: Since the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) remains poor, identification of miRNA as a potential prognostic biomarker for HSCC may help improve personalized therapy. In the 2 cohorts with a total of 511 patients with HSCC (discovery: N = 372 and validation: N = 139) after post-operative radiotherapy, we used miRNA microarray and qRT-PCR to screen out the significant miRNAs which might predict survival. Associations of miRNAs and the signature score of these miRNAs with survival were performed by Kaplan-Meier survival analysis and multivariate Cox hazard model. Among 9 candidate, miRNAs, miR-200a-3p, miR-30b-5p, miR-3161, miR-3605-5p, miR-378b and miR-4451 were up-regulated, while miR-200c-3p, miR-429 and miR-4701 were down-regulated after validation. Moreover, the patients with high expression of miR-200a-3p, miR-30b-5p and miR-4451 had significantly worse overall survival (OS) and disease-specific survival (DSS) than did those with low expression (log-rank P < .05). Patients with a high-risk score had significant worse OS and DSS than those with low-risk score. Finally, after adjusting for other important prognostic confounders, patients with high expression of miR-200a-3p, miR-30b-5p and miR-4451 had significantly high risk of overall death and death owing to HSCC and patients with a high-risk score has approximately 2-fold increased risk in overall death and death owing to HSCC compared with those with a low-risk score. These findings indicated that the 3-miRNA-based signature may be a novel independent prognostic biomarker for patients given surgery and post-operative radiotherapy, supporting that these miRNAs may jointly predict survival of HSCC.

SUBMITTER: Xu X

PROVIDER: S-EPMC6850940 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A 3-miRNA signature predicts survival of patients with hypopharyngeal squamous cell carcinoma after post-operative radiotherapy.

Xu Xinbo X Lu Zhongming Z Gross Neil N Li Guojun G Zhang Fenghua F Lei Dapeng D Pan Xinliang X

Journal of cellular and molecular medicine 20191002 12

Since the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) remains poor, identification of miRNA as a potential prognostic biomarker for HSCC may help improve personalized therapy. In the 2 cohorts with a total of 511 patients with HSCC (discovery: N = 372 and validation: N = 139) after post-operative radiotherapy, we used miRNA microarray and qRT-PCR to screen out the significant miRNAs which might predict survival. Associations of miRNAs and the signature score of these miRNAs with s ...[more]

PMID: 31578816

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Project description:Objective:We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). Results:With cut-off criteria of P < 0.05 and |log2FC|?>?1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan-Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. Conclusions:Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.

Dataset Information

A 3-miRNA signature predicts survival of patients with hypopharyngeal squamous cell carcinoma after post-operative radiotherapy.

Publications

A 3-miRNA signature predicts survival of patients with hypopharyngeal squamous cell carcinoma after post-operative radiotherapy.

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