Dataset Information

Gene set enrichment analysis and meta-analysis identified 12 key genes regulating and controlling the prognosis of lung adenocarcinoma.

ABSTRACT: The aim of the present study was to analyze lung adenocarcinoma-associated microarray data and identify potentially crucial genes. The gene expression profiles were downloaded from the Gene Expression Omnibus database and 6 datasets, of which 2 were discarded and 4 were retained, were preprocessed using packages in the R computing language. Subsequently, Gene Set Enrichment Analysis (GSEA) and meta-analysis was used to screen the common pathways and differentially expressed genes at the transcriptional level. The genes detected from GSEA through The Cancer Genome Atlas databases were subsequently examined, and the crucial genes by survival data were identified. Pathways of the crucial genes were obtained using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the online website Database for Annotation, Visualization and Integrated Discovery (DAVID) tool, and the pathways of crucial genes that were upregulated or downregulated were matched using the Venn method to identify the common crucial pathways. Furthermore, on the basis of the common crucial pathways, key genes that are closely associated with the development and progression of lung adenocarcinoma were identified with the KEGG pathway of DAVID. Additional information was obtained through Gene Ontology annotation. A total of two key pathways, including cell cycle and DNA replication, as well as 12 key genes [DNA polymerase ? subunit 2, DNA replication licensing factor MCM4, MCM6, mitotic checkpoint serine/threonine-protein kinase BUB1, BUB1?, mitotic spindle assembly checkpoint protein MAD2A, dual specificity protein kinase TTK, M-phase inducer phosphatase 1, cell division control protein 45 homolog, cyclin-dependent kinase inhibitor 1C, pituitary tumor-transforming gene 1 protein and polo-like kinase 1] were identified. These key pathways and genes may be studied in future studies involving gene transfection/knockdown, which may provide insights into the prognosis of lung adenocarcinoma. Additional studies are required to confirm their biological function.

SUBMITTER: He W

PROVIDER: S-EPMC6507356 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Gene set enrichment analysis and meta-analysis identified 12 key genes regulating and controlling the prognosis of lung adenocarcinoma.

He Wenwu W Fu Liangmin L Yan Qunlun Q Zhou Qiuxi Q Yuan Kun K Chen Linxin L Han Yongtao Y

Oncology letters 20190409 6

The aim of the present study was to analyze lung adenocarcinoma-associated microarray data and identify potentially crucial genes. The gene expression profiles were downloaded from the Gene Expression Omnibus database and 6 datasets, of which 2 were discarded and 4 were retained, were preprocessed using packages in the R computing language. Subsequently, Gene Set Enrichment Analysis (GSEA) and meta-analysis was used to screen the common pathways and differentially expressed genes at the transcri ...[more]

PMID: 31186783

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Project description:BACKGROUND:Gene Set Enrichment Analysis (GSEA) is a powerful tool to identify enriched functional categories of informative biomarkers. Canonical GSEA takes one-dimensional feature scores derived from the data of one platform as inputs. Numerous extensions of GSEA handling multimodal OMIC data are proposed, yet none of them explicitly captures combinatorial relations of feature scores from multiple platforms. RESULTS:We propose multivariate GSEA (MGSEA) to capture combinatorial relations of gene set enrichment among multiple platform features. MGSEA successfully captures designed feature relations from simulated data. By applying it to the scores of delineating breast cancer and glioblastoma multiforme (GBM) subtypes from The Cancer Genome Atlas (TCGA) datasets of CNV, DNA methylation and mRNA expressions, we find that breast cancer and GBM data yield both similar and distinct outcomes. Among the enriched functional categories, subtype-specific biomarkers are dominated by mRNA expression in many functional categories in both cancer types and also by CNV in many functional categories in breast cancer. The enriched functional categories belonging to distinct combinatorial patterns are involved different oncogenic processes: cell proliferation (such as cell cycle control, estrogen responses, MYC and E2F targets) for mRNA expression in breast cancer, invasion and metastasis (such as cell adhesion and epithelial-mesenchymal transition (EMT)) for CNV in breast cancer, and diverse processes (such as immune and inflammatory responses, cell adhesion, angiogenesis, and EMT) for mRNA expression in GBM. These observations persist in two external datasets (Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) for breast cancer and Repository for Molecular Brain Neoplasia Data (REMBRANDT) for GBM) and are consistent with knowledge of cancer subtypes. We further compare the characteristics of MGSEA with several extensions of GSEA and point out the pros and cons of each method. CONCLUSIONS:We demonstrated the utility of MGSEA by inferring the combinatorial relations of multiple platforms for cancer subtype delineation in three multi-OMIC datasets: TCGA, METABRIC and REMBRANDT. The inferred combinatorial patterns are consistent with the current knowledge and also reveal novel insights about cancer subtypes. MGSEA can be further applied to any genotype-phenotype association problems with multimodal OMIC data.

Dataset Information

Gene set enrichment analysis and meta-analysis identified 12 key genes regulating and controlling the prognosis of lung adenocarcinoma.

Publications

Gene set enrichment analysis and meta-analysis identified 12 key genes regulating and controlling the prognosis of lung adenocarcinoma.

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