MicroRNA expression integrated analysis and identification of novel biomarkers in small cell lung cancer: a meta-analysis

Dandan Han; Lailing Li; Xin Ge; Dan Li; Xiaolei Zhang

doi:10.21037/tcr.2020.04.12

MicroRNA expression integrated analysis and identification of novel biomarkers in small cell lung cancer: a meta-analysis

Transl Cancer Res. 2020 May;9(5):3339-3353. doi: 10.21037/tcr.2020.04.12.

Authors

Dandan Han¹, Lailing Li², Xin Ge¹, Dan Li¹, Xiaolei Zhang¹

Affiliations

¹ Department of Blood Transfusion, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of China, Hefei 230031, China.
² Pneumology Department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of China, Hefei 230031, China.

Abstract

Background: Small cell lung cancer (SCLC) is an aggressive and recalcitrant cancer. In recent years, studies focused on the abnormal expression of microRNA which has proven valuable in terms of prognosis, diagnosis and treatment in SCLC. To address the limitations of independent studies data, a meta-analysis seems necessary for further exploration of microRNA as biological target and regulatory factor in SCLC.

Methods: We performed comprehensive literature retrieval in GEO database and EBI ArrayExpress database. The microRNA expression data was extracted from 4 related researches (GSE15008, GSE74190, GSE19945, GSE77380), which was obtained from GEO database. In each included study, the R. Affymetrix Expression Console's Limma package and RMA algorithms were used to screen for raw data for gene chip quality control, standardization, log2 conversion and differential expression of the gene chip, respectively. Significant microRNA meta-signatures were identified by Robust Rank Aggregation method. Subsequently, gene ontology (GO) enrichment analysis and pathway analysis were performed using bioinformatics tools.

Results: We found a significant microRNA meta-signature of six up-regulated (hsa-miR-182-5p, hsa-miR-96-5p, hsa-miR-7-5p, hsa-miR-301b-3p, hsa-miR-130b-3p, hsa-miR-210-3p) and four down-regulated (hsa-miR-126-3p, hsa-miR-451a, hsa-miR-145-5p, hsa-miR-486-5p) microRNA s in meta-analysis approaches. GO analysis showed that target gene of meta-signatures microRNA was mainly enriched in endosome, chordate embryonic development and transforming growth factor beta receptor. The related functional gene of microRNA meta signature synergistically targeting SCLC signaling pathway was confirmed by enrichment analysis. In particular, neurotrophin and TGF-beta signaling pathway play the most important roles in the pathway network.

Conclusions: Our study identified 10 highly significant and consistently dysregulated microRNA s from 4 datasets, which offering convincing molecular targets and regulatory factors in future research of SCLC.

Keywords: biomarker; meta-analysis; microRNA; small cell lung cancer (SCLC).