Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Comparative genomic hybridization of normal karyotype lung tumors from heavy smokers using Affymetrix SNP arrays

ABSTRACT: Whole genome analysis on normal karyotype lung tumors from heavy smokers.
Our study regarded a population of 5203 heavy smokers volunteers, enrolled in a screening program set up at the European Institute of Oncology. Each volunteer yearly undergoes low dose CT-scan. At the end of the second year, among 89 screening-identified patients with lung cancers, 57 cases with clinical localized lung malignancy were evaluated for the present analysis. These, together with 21 other asymptomatic patients (pilot population), carrying non-screening detected lung cancers, but with same characteristics of the screened population (asymptomatic, smokers, older than 50, with an occasionally detected localized cancer), constituted our study population (78 cases). At the time of surgical resection, a portion of the tumoral tissue was collected, snap-frozen and stored at -80 C, for the subsequent tumor cellularity evaluation and DNA extraction. Tumor cellularity was determined by analyzing ematossilin-eosin stained sections of the tumor samples. The evaluation was carried out by a pathologist of the Molecular Pathology Unit, at the IFOM-IEO campus. Only NK samples with an evaluated tumor cellularity of at least 70% were used for the high-resolution genomic analysis: this allowed us to restrict normal cells contamination of the tumor genome pattern in our analysis. A genomic macroscopic analysis was carried out in order to identify tumors harboring a normal karyotype, which were then subjected to a high-resolution genomic analysis, through the Affymetrix SNPs technology.

ORGANISM(S): Homo sapiens

DISEASE(S): normal tissue

SUBMITTER: Elena Belloni

PROVIDER: E-MEXP-2450 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure. We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change>1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p=0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers. Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers. Experiment Overall Design: Overall, 180 adenocarcinoma and non-tumor tissue samples were selected for the analyses, including duplicate or triplicate samples from 14 subjects for quality control. From the original 180 samples, 148 provided sufficient quantity of high-quality RNA for microarray analyses; 13 additional samples were excluded because of problematic assays. Normalization was conducted on the remaining 135 microarrays. After normalization, 13 samples were excluded because of low percentage of tumor cells in the tumor tissues. This report is based on 122 samples, of which 15 duplicates were averaged, resulting in 107 final expression values from 58 tumor and 49 non-tumor tissues from 20 never smokers, 26 former smokers, and 28 current smokers.

Dataset Information

Comparative genomic hybridization of normal karyotype lung tumors from heavy smokers using Affymetrix SNP arrays

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure