J Cancer 2019; 10(23):5793-5804. doi:10.7150/jca.30336

Research Paper

Prognostic Value of Survival of MicroRNAs Signatures in Non-small Cell Lung Cancer

Bo Chen1,2, Tianshun Gao3, Weiwei Yuan1, Weihong Zhao1, Tza-Huei Wang2,4,5,6✉, Jianqing Wu1✉

1. Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China.
2. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
3. Wilmer Bioinformatics, Johns Hopkins Hospital, Baltimore, Maryland 21231, USA.
4. Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
5. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
6. Johns Hopkins Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, USA.

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Citation:
Chen B, Gao T, Yuan W, Zhao W, Wang TH, Wu J. Prognostic Value of Survival of MicroRNAs Signatures in Non-small Cell Lung Cancer. J Cancer 2019; 10(23):5793-5804. doi:10.7150/jca.30336. Available from http://www.jcancer.org/v10p5793.htm

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Abstract

Introduction: Accumulating evidence showed that a large number of microRNAs (miRNAs) are abnormally expressed in lung cancer tissues and play critical roles in cancer development and progression. The aim of this study is to identify the differentially expressed miRNAs (DEMs) between non-small cell lung cancer (NSCLC) and normal lung tissues, and evaluate the prognostic value and potential target gene functional enrichment of the DEMs. Materials and Methods: We first downloaded the high-throughput miRNA data from The Cancer Genome Atlas Project (TCGA) database, and subsequently analyzed the data using bioinformatics analysis including limma package in R, Kaplan-Meier curve and Log-rank method, and several online analysis tools. Results: A total of 125 DEMs and 138 DEMs were respectively identified in lung adenocarcinoma (LUAD) tissues and lung squamous cell carcinoma (LUSC) tissues compared with their matched normal tissues. Moreover, we found that the prognostic function of the eight miRNAs (miR-375, miR-148a, miR-29b-1 and miR-584 for LUAD; miR-4746, miR-326, miR-93 and miR-671 for LUSC). Furthermore, the two four-miRNA signatures were constructed and found to be an independent prognostic factor for LUAD and LUSC patients, respectively. Additionally, our results indicated that the target genes of eight miRNAs may be involved in various pathways related to NSCLC, including PI3K-Akt, TGF-beta, FoxO, Ras, GPI-anchor biosynthesis and metabolic, Rap1, HIF-1 and proteasome. Conclusion: Overall, eight miRNAs were closely correlated with survival of NSCLC patients, and the constructed two four-miRNA signatures could be respectively used as prognostic markers in LUAD and LUSC patients.

Keywords: MicroRNAs, Non-small cell lung cancer, Survival analysis, Prognostic value, Functional enrichment