Analysis of orthologous gene expression between human pulmonary adenocarcinoma and a carcinogen-induced murine model.
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 approximately 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. The eicosanoid pathway enzymes prostacyclin synthase (PGIS) and inducible prostaglandin E(2) 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.
Stearman
Robert S
RS
Department of Medicine/Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, USA. robert.stearman@uchsc.edu
Dwyer-Nield
Lori
L
Zerbe
Laura
L
Blaine
Stacy A
SA
Chan
Zeng
Z
Bunn
Paul A
PA
Johnson
Gary L
GL
Hirsch
Fred R
FR
Merrick
Daniel T
DT
Franklin
Wilbur A
WA
Baron
Anna E
AE
Keith
Robert L
RL
Nemenoff
Raphael A
RA
Malkinson
Alvin M
AM
Geraci
Mark W
MW
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D002273:Carcinogens; D016000:Cluster Analysis; D004261:DNA Replication / Q000235:genetics; D030561:Databases, Nucleic Acid; D004195:Disease Models, Animal; D004798:Enzymes / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009389:Neovascularization, Pathologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D013045:Species Specificity
D002273:Carcinogens; D004798:Enzymes