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Gene expression profiles of NSCLC tumors

ABSTRACT: A custom microarray was used to measure the gene expression of NSCLC tumors. This represents a subset of samples which also have matched DNA copy number profiles from array CGH experiments

ORGANISM(S): Homo sapiens

PROVIDER: GSE31799 | GEO | 2011/09/12

SECONDARY ACCESSION(S): PRJNA155047

REPOSITORIES: GEO

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Gene expression profiles of NSCLC tumors

Project description:A custom microarray was used to measure the gene expression of NSCLC tumors. This represents a subset of samples which also have matched DNA copy number profiles from array CGH experiments 49 microdissected NSCLC tumor samples

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Project description:Non-small cell lung cancer (NSCLC) presents a notoriously genomically unstable cancer type, with numerous large scale and focal genomic aberrations resulting in gene copy number variations across the whole genome. The relations of these gene copy number changes to subsequent mRNA levels are only fragmentarily understood. The aim of this study was an integrated analysis of gene copy number changes and corresponding gene expression in a large clinically annotated NSCLC patient cohort. Fresh frozen tumor sample from 190 resected NSCLC patients were subjected to SNP arrays and gene expression array analysis resulting 39788 tested copy number/ RNA expression pairs. Correlation analysis using an externally centered correlation coefficient (ECCC) revealed that gene expression of 19058 genes was significantly influenced by gene copy number changes (FDR < 0.05). However, only 440 probe sets demonstrated high correlations (ECCC > 0.7) that were mostly due to few cases with high gene copy number gains. These gene copy number dependent genes were clustered in only few chromosomal hot spot regions and classical oncogenes (e.g. EGFR, MDM2, KRAS) are overrepresented among these genes. In a meta-analysis, including 1585 NSCLC patients, gene expression levels from 70 of 440 (16%) gene-copy-number-dependent genes were associated with survival. In conclusion, the genome-wide analysis indicates that gene copy number aberrations influence directly gene expression levels in a distinct subset of genes. The concrete illustration of these molecular relations help to interpret the impact of gene copy number changes and may serve as starting points to identify new cancer drivers in NSCLC.

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