Gene expression-based classification of non-small cell lung carcinomas and survival prediction

• Published in: PloS one 2010-04, Vol.5 (4), p.e10312-e10312
• Main Authors: Hou, Jun, Aerts, Joachim, den Hamer, Bianca, van Ijcken, Wilfred, den Bakker, Michael, Riegman, Peter, van der Leest, Cor, van der Spek, Peter, Foekens, John A, Hoogsteden, Henk C, Grosveld, Frank, Philipsen, Sjaak
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Bioinformatics; Biology; Breast cancer; Cancer; Cancer genetics; Carcinoma, Non-Small-Cell Lung - classification; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Case-Control Studies; Cell survival; Classification; Colorectal cancer; Correlation analysis; Epidermal growth factor; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genes, Neoplasm; Genomes; Genomics; Histology; Humans; Kaplan-Meier Estimate; Lung cancer; Lung carcinoma; Lung diseases; Male; Medical prognosis; Medical research; Metastasis; Middle Aged; Molecular Biology/Bioinformatics; Neural Networks (Computer); Non-small cell lung cancer; Non-small cell lung carcinoma; Oncology/Lung Cancer; Pathology; Pathology/Molecular Pathology; Patient outcomes; Patients; Precision Medicine - methods; Predictive Value of Tests; Prognosis; Protein expression; Risk groups; RNA, Neoplasm - analysis; Signatures; Small cell lung carcinoma; Studies; Surgery; Survival; Survival analysis; Survival Rate; Therapy; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010312

Current clinical therapy of non-small cell lung cancer depends on histo-pathological classification. This approach poorly predicts clinical outcome for individual patients. Gene expression profiling holds promise to improve clinical stratification, thus paving the way for individualized therapy. A genome-wide gene expression analysis was performed on a cohort of 91 patients. We used 91 tumor- and 65 adjacent normal lung tissue samples. We defined sets of predictor genes (probe sets) with the expression profiles. The power of predictor genes was evaluated using an independent cohort of 96 non-small cell lung cancer- and 6 normal lung samples. We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of non-small cell lung cancer. Correlation analysis identified 17 genes which showed the best association with post-surgery survival time. This signature was used for stratification of all patients in two risk groups. Kaplan-Meier survival curves show that the two groups display a significant difference in post-surgery survival time (p = 5.6E-6). The performance of the signatures was validated using a patient cohort of similar size (Duke University, n = 96). Compared to previously published prognostic signatures for NSCLC, the 17 gene signature performed well on these two cohorts. The gene signatures identified are promising tools for histo-pathological classification of non-small cell lung cancer, and may improve the prediction of clinical outcome.