Research Papers:
Non-small cell lung cancer associated microRNA expression signature: integrated bioinformatics analysis, validation and clinical significance
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Abstract
Chunyu Li1, Yunhong Yin1, Xiao Liu1, Xuejiao Xi1, Weixiao Xue1, Yiqing Qu1
1Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan 250012, China
Correspondence to:
Yiqing Qu, email: [email protected]
Keywords: NSCLC, microRNA, robust rank aggregation, integrative analysis, biomarker
Received: December 23, 2016 Accepted: February 13, 2017 Published: February 21, 2017
ABSTRACT
Recently, increasing studies of miRNA expression profiling has confirmed that miRNA plays an essential role in non-small cell lung cancer (NSCLC). However, inconsistent or discrepant results exist in these researches. In present study, we performed an integrative analysis of 32 miRNA profiling studies compared the differentially expressed miRNA between NSCLC tissue and non-cancerous lung tissue to identify candidate miRNAs associated with NSCLC. 7 upregulated and 10 downregulated miRNAs were identified as miRNA integrated-signature using Robust Rank Aggregation (RRA) method. qRT-PCR demonstrated that miR-21-5p, miR-210, miR-205-5p, miR-182-5p, miR-31-5p, miR-183-5p and miR-96-5p were up-regulated, whereas miR-126-3p, miR-30a-5p, miR-451a, miR-143-3p and miR-30d-5p were down-regulated more than 2 folds in the NSCLC, which was further validated in Tumor Cancer Genome Atlas (TCGA) database. Receiver operating characteristic (ROC) curve analysis confirmed that 9 miRNAs had good predictive performance (AUC > 0.9). Cox regression analysis revealed that miR-21-5p (hazard ratio [HR]: 1.616, 95% CI: 1.114–2.342, p = 0.011) and miR-30d-5p (HR: 0.578, 95% CI: 0.400–0.835, p = 0.003) were independent prognostic factors in NSCLC for overall survival. The accumulative effects of the two miRNAs on the prognosis of NSCLC were further estimated. The results showed that patients with two positive markers had a worse prognosis than those with one or none positive marker. In conclusion, this study contributes to the comprehension of the role of miRNAs in NSCLC and provides a basis for further clinical application.
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PII: 15596