Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model

Robert S. Stearman, Lori Dwyer-Nield, Laura Zerbe, Stacy A. Blaine, Zeng Chan, Paul A. Bunn, Gary L. Johnson, Fred R. Hirsch, Daniel T. Merrick, Wilbur A. Franklin, Anna E. Baron, Robert L. Keith, Raphael A. Nemenoff, Alvin M. Malkinson, Mark W. Geraci

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

Abstract

Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer, and its absolute incidence is increasing dramatically. Compared to human lung AC, the A/J mouse-urethane model exhibits similar histological appearance and molecular changes. We examined the gene expression profiles of human and murine lung tissues (normal or AC) and compared the two species' datasets after aligning ∼7500 orthologous genes. A list of 409 gene classifiers (P value <0.0001), common to both species (joint classifiers), showed significant, positive correlation in expression levels between the two species. A number of previously reported expression changes were recapitulated in both species, such as changes in glycolytic enzymes and cell-cycle proteins. Unexpectedly, joint classifiers in angiogenesis were uniformly down-regulated in tumor tissues. he eicosanoid pathway enzymes prostacyclin synthase (PGIS) and inducible prostaglandin E2 synthase (PGES) were joint classifiers that showed opposite effects in lung AC (PGIS down-regulated; PGES up-regulated). Finally, tissue microarrays identified the same protein expression pattern for PGIS and PGES in 108 different non-small cell lung cancer biopsies, and the detection of PGIS had statistically significant prognostic value in patient survival. Thus, the A/J mouse-urethane model reflects significant molecular details of human lung AC, and comparison of changes in orthologous gene expression may provide novel insights into lung carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1763-1775
Number of pages13
JournalAmerican Journal of Pathology
Volume167
Issue number6
DOIs
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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