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Integrated analysis profiles of long non-coding RNAs reveal potential biomarkers of drug resistance in lung cancer.

ABSTRACT: Lung cancer is one of the leading causes of cancer-related death. Resistance to chemotherapy and molecularly targeted therapies is a major problem that can contribute substantially to high mortality. The roles of long non-coding RNAs (lncRNAs) in drug resistance of lung cancer are insufficiently understood. Here, we identified a distinct drug resistance-related transcriptional signature and constructed a functional lncRNA-mRNA co-expression network. We found that 34 lncRNAs and 103 mRNAs have differential expression in drug resistance of lung cancer, in which 10 lncRNAs were down regulated and 24 up regulated; 49 mRNAs were down regulated and 54 up regulated. LncRNAs-mRNAs expression network analysis revealed a role for lncRNAs in modulating cancer-related pathways. We also found that two pair lncRNAs and their subnetworks were highly related to drug resistance. NR_028502.1/NR_028505.1 were found differentially co-expressed with nine mRNAs, and highly correlated with better clinical outcome. NR_030725.1/NR_030726.1 co-expressed with eleven mRNAs, and were associated with poor survival in patients with lung cancer. Our work comprehensively identified expression signature of resistance-associated lncRNAs and their inter-regulated mRNAs in lung cancer.

SUBMITTER: Xue W

PROVIDER: S-EPMC5609887 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Integrated analysis profiles of long non-coding RNAs reveal potential biomarkers of drug resistance in lung cancer.

Xue Wenhua W Li Lifeng L Tian Xin X Fan Zhirui Z Yue Ying Y Zhang Chaoqi C Ding Xianfei X Song Xiaoqin X Ma Bingjun B Zhai Yunkai Y Lu Jingli J Kan Quancheng Q Zhao Jie J

Oncotarget 20170322 38

Lung cancer is one of the leading causes of cancer-related death. Resistance to chemotherapy and molecularly targeted therapies is a major problem that can contribute substantially to high mortality. The roles of long non-coding RNAs (lncRNAs) in drug resistance of lung cancer are insufficiently understood. Here, we identified a distinct drug resistance-related transcriptional signature and constructed a functional lncRNA-mRNA co-expression network. We found that 34 lncRNAs and 103 mRNAs have di ...[more]

PMID: 28968955

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Project description:BackgroundWhile lung cancer patient outcomes are well-recognized to vary as a function of patient sex, there has been insufficient research regarding the relationship between patient sex and EGFR(Epidermal growth factor receptor) response efficacy. The present study therefore sought to identify novel sex-related biomarkers of bevacizumab/erlotinib (BE) responses in non-small cell lung cancer (NSCLC) patients.MethodsThe exon array data in the Gene Expression Omnibus (GEO) dataset were analyzed in order to identify patterns of mRNA and lncRNA expression associated with BE resistance in NSCLC. These differentially expressed (DE) lncRNAs and mRNAs were identified via DE Analysis Filtering. These DE mRNAs were then assessed for their potential functional roles via pathway enrichment analyses, with overlapping functions possibly associated with the BE resistance. The mRNAs in these overlapping groups were then assessed for their correlations with patient survival, and lncRNA-mRNA co-expression networks were generated for each patient subset. A protein-protein interaction (PPI) network was also generated based upon these DE mRNAs.ResultsIn females we identified 172 DE lncRNAs and 1766 DE mRNAs associated with BE responses, while in males we identified 78 DE lncRNAs and 485 DE mRNAs associated with such responses. Based on the overlap between these two datasets, we identified a total of 37 GO functions and 18 pathways associated with BE responses. Co-expression and PPI networks suggested that the key lncRNAs and mRNAs associated with these BE response mechanisms weredifferent in the male and female patients.ConclusionsThis work is the first to conduct a global profiling of the relationship between lncRNA and mRNA expression patterns, patient sex, and BE responses in individuals suffering from NSCLC. Together these results suggest that the integrative lncRNA-mRNA expression analyses may offer invaluable new therapeutic insights that can guide the tailored treatment of lung cancer in order to ensure optimal BE responses.

Dataset Information

Integrated analysis profiles of long non-coding RNAs reveal potential biomarkers of drug resistance in lung cancer.

Publications

Integrated analysis profiles of long non-coding RNAs reveal potential biomarkers of drug resistance in lung cancer.

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