Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer
Autor: | Jabs, Verena, Edlund, Karolina, König, Helena, Grinberg, Marianna, Madjar, Katrin, Rahnenführer, Jörg, Ekman, Simon, Bergkvist, Michael, Holmberg, Lars, Ickstadt, Katja, Botling, Johan, Hengstler, Jan G., Micke, Patrick |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
Lung Neoplasms
Gene Dosage Gene Expression lcsh:Medicine Research and Analysis Methods Carcinomas Lung and Intrathoracic Tumors Mathematical and Statistical Techniques Cancer Genomics Genomic Medicine Adenocarcinomas Carcinoma Non-Small-Cell Lung Basic Cancer Research Genetics Medicine and Health Sciences Humans Statistical Methods lcsh:Science Cancer och onkologi Gene ontologies Non-small cell lung cancer Squamous cell carcinomas Gene expression Cancer genomics Meta-analysis Clinical Laboratory Medicine Gene Ontologies lcsh:R Biology and Life Sciences Cancers and Neoplasms Computational Biology Squamous Cell Carcinomas Genomics Genome Analysis Survival Analysis Non-Small Cell Lung Cancer Gene Expression Regulation Neoplastic Klinisk laboratoriemedicin Oncology Cancer and Oncology Physical Sciences lcsh:Q Mathematics Statistics (Mathematics) Research Article Meta-Analysis |
Zdroj: | PLoS ONE, Vol 12, Iss 11, p e0187246 (2017) PLoS ONE PLOS ONE, 12(11):e0187246 |
ISSN: | 1932-6203 |
Popis: | Non-small cell lung cancer (NSCLC) represents a genomically unstable cancer type with extensive copy number aberrations. The relationship of gene copy number alterations and subsequent mRNA levels has only fragmentarily been described. The aim of this study was to conduct a genome-wide analysis of gene copy number gains and corresponding gene expression levels in a clinically well annotated NSCLC patient cohort (n = 190) and their association with survival. While more than half of all analyzed gene copy number-gene expression pairs showed statistically significant correlations (10,296 of 18,756 genes), high correlations, with a correlation coefficient >0.7, were obtained only in a subset of 301 genes (1.6%), including KRAS, EGFR and MDM2. Higher correlation coefficients were associated with higher copy number and expression levels. Strong correlations were frequently based on few tumors with high copy number gains and correspondingly increased mRNA expression. Among the highly correlating genes, GO groups associated with posttranslational protein modifications were particularly frequent, including ubiquitination and neddylation. In a meta-analysis including 1,779 patients we found that survival associated genes were overrepresented among highly correlating genes (61 of the 301 highly correlating genes, FDR adjusted p |
Databáze: | OpenAIRE |
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