Integrative Bioinformatics Analysis Reveals Potential Long Non-Coding RNA Biomarkers and Analysis of Function in Non-Smoking Females with Lung Cancer

BACKGROUND: Lung cancer is the most lethal cancer worldwide. The aim of this study was to identify the tumor-related lncRNAs and explore their functions in female non-smokers with lung cancer. MATERIAL/METHODS: The gene expression microarray datasets GSE19804, GSE31210, and GSE31548 were downloaded from the Gene Expression Omnibus database. The differentially-expressed lncRNAs between non-smoking female lung cancer samples and non-tumor lung tissues were identified using GEO2R. RESULTS: In total, 25, 40, and 15 differentially-expressed lncRNAs were obtained from GSE19804, GSE31210, and GSE31548 datasets (|logFC| >1, adj. P<0.05), respectively. Eight lncRNAs were screened out in all 3 datasets. Of these, 5 lncRNAs were up-regulated and 3 lncRNAs were down-regulated in lung cancer tissues compared to non-tumor lung tissues. Then, the target miRNAs of aberrantly expressed lncRNAs and target mRNAs corresponding to miRNAs were predicted. Subsequently, the ceRNA network with 8 key lncRNAs, 20 miRNAs, and 38 mRNAs were constructed. Functional and pathway enrichment analysis showed these target genes were mainly enriched in biological processes associated with protein binding, nucleus, metal ion binding, regulation of transcription from RNA polymerase II promoter, nucleic acid binding, cell differentiation, microRNAs in cancer, and the hippo signaling pathway. Survival analysis of these lncRNAs revealed that low LINC00968 (P=0.0067) and TBX5-AS1 (P=0.0028) expression were associated with unfavorable prognosis in never-smoking female lung cancer patients. CONCLUSIONS: The present study promotes understanding of the molecular mechanism of the pathogenesis of non-smoking female lung cancer and provides potential biomarkers for diagnosis and treatment.