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Originally published In Press as doi:10.1074/mcp.M200008-MCP200 on March 12, 2002.
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Molecular & Cellular Proteomics 1:304-313, 2002.
© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


Research

Discordant Protein and mRNA Expression in Lung Adenocarcinomas *

Guoan Chen{ddagger}, Tarek G. Gharib{ddagger}, Chiang-Ching Huang§, Jeremy M. G. Taylor§, David E. Misek, Sharon L. R. Kardia||, Thomas J. Giordano**, Mark D. Iannettoni{ddagger}, Mark B. Orringer{ddagger}, Samir M. Hanash and David G. Beer{ddagger},{ddagger}{ddagger}

{ddagger} Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109
§ Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109
|| Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109
** Department of Pathology,University of Michigan, Ann Arbor, Michigan 48109
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109

The relationship between gene expression measured at the mRNA level and the corresponding protein level is not well characterized in human cancer. In this study, we compared mRNA and protein expression for a cohort of genes in the same lung adenocarcinomas. The abundance of 165 protein spots representing 98 individual genes was analyzed in 76 lung adenocarcinomas and nine non-neoplastic lung tissues using two-dimensional polyacrylamide gel electrophoresis. Specific polypeptides were identified using matrix-assisted laser desorption/ionization mass spectrometry. For the same 85 samples, mRNA levels were determined using oligonucleotide microarrays, allowing a comparative analysis of mRNA and protein expression among the 165 protein spots. Twenty-eight of the 165 protein spots (17%) or 21 of 98 genes (21.4%) had a statistically significant correlation between protein and mRNA expression (r > 0.2445; p < 0.05); however, among all 165 proteins the correlation coefficient values (r) ranged from -0.467 to 0.442. Correlation coefficient values were not related to protein abundance. Further, no significant correlation between mRNA and protein expression was found (r = -0.025) if the average levels of mRNA or protein among all samples were applied across the 165 protein spots (98 genes). The mRNA/protein correlation coefficient also varied among proteins with multiple isoforms, indicating potentially separate isoform-specific mechanisms for the regulation of protein abundance. Among the 21 genes with a significant correlation between mRNA and protein, five genes differed significantly between stage I and stage III lung adenocarcinomas. Using a quantitative analysis of mRNA and protein expression within the same lung adenocarcinomas, we showed that only a subset of the proteins exhibited a significant correlation with mRNA abundance.


{ddagger}{ddagger} To whom correspondence should be addressed: General Thoracic Surgery, SRB II, B560, Box 0686, University of Michigan Medical School, Ann Arbor, MI 48109-086; E-mail: dgbeer{at}umich.edu


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