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Integrated genome-wide analysis of gene dosage and gene expression in Non Small Cell Lung Cancer

ABSTRACT: Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease. We examined the effect of chromosomal copy number changes on gene expression in resected NSCLC patients. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90AA1, residing on 14q32. This deletion was correlated with better overall and recurrence free survival (P=0.008 and P=0.004, respectively) and survival was also longer in patients whose tumors had low expression levels of HSP90AA1. We extended the analysis to an independent validation set of 140 resected NSCLC patients, and confirmed low HSP90AA1 expression to be significantly related with overall survival and recurrence free survival (P=0.003 and P=0.007, respectively). In vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. We suggest that targeting HSP90 will have clinical impact for NSCLC patients. Keywords: Array CGH gene expression integration

ORGANISM(S): Homo sapiens

PROVIDER: GSE7878 | GEO | 2007/08/01

SECONDARY ACCESSION(S): PRJNA99907

REPOSITORIES: GEO

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2022-05-01 | GSE198957 | GEO

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2012-03-26 | E-GEOD-29135 | biostudies-arrayexpress

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Retrospective and prospective validation of a 33-gene signature to predict recurrence of lung cancer after surgery.

Project description:We developed a 33-gene signature that is strongly correlated to the time to recurrence in non-small cell lung cancer (NSCLC). The signature was validated retrospectively in 5 cohorts of 972 NSCLC patients and in one prospective study of 111 NSCLC Stage IA patients. In all cohorts, and all stages of the disease, the signature identified a rare, aggressive tumor type that had a high proportion of recurrence after surgery and a median survival of 35 months (95% C.I.: 19-58). This tumor type forms a separate cluster in an analysis of the expression of the 33 genes in patient tumors. The signature is associated with cellular processes required by rapidly growing and spreading tumors: cell migration and invasion, vascularization, and response to hypoxia. The signature also identifies patients with good prognosis (median survival 114 months, (95% C.I.: 85-160), and intermediate prognosis (median survival 61 months (95% C. I.: 50-73). The signature is quite robust and works on tumor samples archived in RNAlater, Tissue-Tek, or formalin-fixed and paraffin embedded. 156 samples -------------------------------- *** Submitter has not provided information such as time to recurrence. Thus, the data is incomplete.

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Project description:Study to identify genes associated with NSCLC recurrence in patients not receiving adjuvant chemotherapy. Purpose: Recent clinical trials suggest improvement in survival with adjuvant chemotherapy in non-small cell lung cancer (NSCLC). This study's aim is to identify genes associated with NSCLC recurrence in patients not receiving adjuvant chemotherapy. Experimental design: Banked NSCLC tumors of patients who underwent resection of stage Ia-IIIb disease were identified. Patients were stratified into two groups: recurrent (R, n=11) or non-recurrent (NR, n=16) 2 years after surgery. Microarray profiling and Cox multivariate analysis were performed. Conclusion: Increased CYP3A5 gene expression correlates with NSCLC recurrence and promotes proliferation through mechanisms that may involve, in part, CYP3A5 epoxygenase activity. Keywords: comparison of gene expression profiles for recurrent and non-recurrent cancer

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