Dataset Information

Comprehensive analysis of lncRNA expression profiles and identification of functional lncRNAs in lung adenocarcinoma.

ABSTRACT: Increasing evidence has highlighted the critical roles of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets for cancer. Here, we characterized lncRNA expression profile in lung adenocarcinoma (LUAD). A training-validation method was applied to identify differentially expressed lncRNAs between LUAD samples and normal samples. 856 differentially expressed lncRNAs were identified. Bioinformatics analyses showed that these lncRNAs were located nearby transcription start sites and key regulators of cancer and these lncRNAs were involved in many critical biological processes. We found the lung cancer associated lncRNA 6 (LCAL6) was significantly unregulated and predicted survival in LUAD. Silence of LCAL6 inhibited LUAD tumor cell growth both in vitro and in vivo. To summary, we comprehensively analyze lncRNA expression profile in LUAD and provide resources for further search for clinical biomarkers and therapeutic targets of LUAD.

SUBMITTER: Qiu M

PROVIDER: S-EPMC4941294 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Comprehensive analysis of lncRNA expression profiles and identification of functional lncRNAs in lung adenocarcinoma.

Qiu Mantang M Feng Dongjie D Zhang Haitian H Xia Wenjia W Xu Youtao Y Wang Jie J Dong Gaochao G Zhang Yewei Y Yin Rong R Xu Lin L

Oncotarget 20160301 13

Increasing evidence has highlighted the critical roles of long non-coding RNAs (lncRNAs) as biomarkers and therapeutic targets for cancer. Here, we characterized lncRNA expression profile in lung adenocarcinoma (LUAD). A training-validation method was applied to identify differentially expressed lncRNAs between LUAD samples and normal samples. 856 differentially expressed lncRNAs were identified. Bioinformatics analyses showed that these lncRNAs were located nearby transcription start sites and ...[more]

PMID: 26918601

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Project description:BackgroundFetal adenocarcinoma of the lung is a rare variant of lung adenocarcinoma and is subcategorized into low-grade and high-grade (H-FLAC) fetal adenocarcinoma. We previously reported poor prognosis in pulmonary adenocarcinomas with an H-FLAC component; however, the genetic abnormalities involved in H-FLAC remain unclear. Therefore, this study aimed to elucidate molecular abnormalities as potential therapeutic targets for H-FLACs.MethodsWe performed immunohistochemical analysis and comprehensive genetic analyses using whole-exome sequencing in 16 lung cancer samples with an H-FLAC component. DNA was extracted from formalin-fixed paraffin-embedded tissues after macrodissection of the H-FLAC component.ResultsCancer-related mutations were identified in TP53 (7/16 cases), KMT2C (6/16 cases), KRAS (4/16 cases), NF1 (3/16 cases), STK11 (3/16 cases), CTNNB1 (2/16 cases), and EGFR (1/16 cases). A high tumor mutation burden of ≥10 mutations per megabase was observed in 3/16 cases. A high microsatellite instability was not detected in any case. Based on the cosine similarity with the Catalogue of Somatic Mutations in Cancer mutational signatures, H-FLACs were hierarchically clustered into three types: common adenocarcinoma-like (five cases), surfactant-deficient (ten cases), and signatures 2 and 13-related (one case). All common adenocarcinoma-like cases presented thyroid transcription factor-1 (TTF-1) expression, whereas surfactant-deficient cases often presented loss of TTF-1 and surfactant protein expression and included cases with mutations in the surfactant system genes NKX2-1 and SFTPC. H-FLACs displayed low programmed death ligand-1 (PD-L1) expression (1-49% of tumor cells) in 5/16 cases, and no case displayed high PD-L1 expression (≥50% of tumor cells).ConclusionsThis study indicates that lung cancers with an H-FLAC component rarely harbor currently targetable driver gene mutations for lung cancer but display a high frequency of KMT2C mutations. The microsatellite instability, tumor mutation burden, and PD-L1 expression status suggest a poor response to immune checkpoint therapy.

Project description:Brain metastases originating from lung adenocarcinoma (LAD) occur frequently. The aim of the current study was to assess potential biomarkers for the prognosis of lung adenocarcinoma brain metastasis (LAD-BM) through the analysis of gene expression microarrays. The current study downloaded two gene expression datasets, GSE14108 and GSE10245, from the Gene Expression Omnibus database. From GSE14108 and GSE10245, 19 LAD-BM samples and 40 primary LAD samples were selected for analysis. To identify the differentially expressed genes (DEGs), the current study compared the two sample groups, using the limma R package. Subsequently, pathway enrichment analysis was conducted using the Cluster Profiler R package, and the construction of the protein-protein interaction (PPI) network was executed utilizing the Search Tool for the Retrieval of Interacting Genes database. The microRNA-target network was built using the TargetScore R package. Then, these networks were established and visualized using Cytoscape software. An array of 463 DEGs was identified in the LAD-BM samples, including 256 upregulated and 207 downregulated genes. Based on functional term enrichment analysis using the Gene Ontology database and signaling pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes database, it was identified that the overlapping DEGs were primarily involved in chemokine-associated signal transduction, which may mediate lung cancer cell metastasis to the brain. Chemokine ligand 2, lysozyme, matrix metalloproteinase-2 (MMP-2), lysyl oxidase (LOX) and granzyme B were identified as potential biomarkers according to a topological analysis of the PPI networks. Two notable nodes, MMP-2 and LOX, appeared in the PPI network and were key points in the microRNA-target network, as they were regulated by hsa-let-7d. Many DEGs and microRNAs were regarded as prognostic biomarkers for lung adenocarcinoma metastasis in the current study. These DEGs were primarily associated with chemokine-mediated signaling pathways. In addition, MMP-2 and LOX were predicted to be targets of hsa-let-7d.

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Comprehensive analysis of lncRNA expression profiles and identification of functional lncRNAs in lung adenocarcinoma.

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Comprehensive analysis of lncRNA expression profiles and identification of functional lncRNAs in lung adenocarcinoma.

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