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. 2018 Aug 18:24:5771-5778.
doi: 10.12659/MSM.908884.

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

Affiliations

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

Fang Qiao et al. Med Sci Monit. .

Abstract

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 AND 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.

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Conflict of interest statement

Conflict of interests

None.

Figures

Figure 1
Figure 1
Heat map of differentially expressed lncRNAs in GSE19804 (A), GSE31210 (B), and GSE31548 (C) datasets. Red: up-regulation; green: down-regulation.
Figure 2
Figure 2
Identification of differentially expressed lncRNAs in datasets GSE19804, GSE31210, and GSE31548.
Figure 3
Figure 3
The lncRNA-miRNA-mRNA ceRNA network. Red diamonds, miRNAs; Green rectangles, lncRNAs; Orange ovals, mRNAs.
Figure 4
Figure 4
Kaplan-Meier survival curves for LINC00968 and TBX5-AS1 expression in never-smoking female lung cancer patients.

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