Expression signatures of metastatic capacity in a genetic mouse model of lung adenocarcinoma

• Published in: PloS one 2009-04, Vol.4 (4), p.e5401-e5401
• Main Authors: Gibbons, Don L, Lin, Wei, Creighton, Chad J, Zheng, Shuling, Berel, Dror, Yang, Yanan, Raso, Maria Gabriela, Liu, Diane D, Wistuba, Ignacio I, Lozano, Guillermina, Kurie, Jonathan M
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Analysis; Animals; Bioinformatics; Breast cancer; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Biology/Gene Expression; Cell cycle; Data mining; Data processing; Disease Models, Animal; Gender differences; Gene expression; Gene Expression Profiling; Genes; Genes, ras - genetics; Genetic Predisposition to Disease; Genetic transcription; Genetics and Genomics/Gene Expression; Growth factors; Health aspects; Lung cancer; Lung cancer, Non-small cell; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medical diagnosis; Medical prognosis; Metastases; Metastasis; Mice; MicroRNAs; Mutation; Mutation, Missense; Neoplasm Metastasis - genetics; Non-small cell lung carcinoma; Oncology; Oncology/Lung Cancer; Transcription; Tumor proteins; Tumor Suppressor Protein p53 - genetics; Tumors; Validation studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005401

Non-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize. The biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-ras(G12D) and p53(R172H). We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature. These findings provide evidence that K-ras(G12D); p53(R172H) mice recapitulate features of human NSCLC metastasis and will provide a useful platform on which to study the biologic basis for lung adenocarcinoma metastasis and its prevention by novel agents.