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Submitted on January 21, 2002
Revised on March 12, 2002
Accepted on March 12, 2002

Discordant protein and mRNA expression in lung adenocarcinomas

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

Department of Surgery, University of Michigan, Ann Arbor, MI 48109

Corresponding Author: guoanche{at}umich.edu

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 9 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.


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Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L399 - L410.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. ProteomicsHome page
M. Huber, I. Bahr, J. R. Kratzschmar, A. Becker, E.-C. Muller, P. Donner, H.-D. Pohlenz, M. R. Schneider, and A. Sommer
Comparison of Proteomic and Genomic Analyses of the Human Breast Cancer Cell Line T47D and the Antiestrogen-resistant Derivative T47D-r
Mol. Cell. Proteomics, January 1, 2004; 3(1): 43 - 55.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
G. Chen, T. G Gharib, H. Wang, C.-C. Huang, R. Kuick, D. G. Thomas, K. A. Shedden, D. E. Misek, J. M. G. Taylor, T. J. Giordano, et al.
Protein profiles associated with survival in lung adenocarcinoma
PNAS, November 11, 2003; 100(23): 13537 - 13542.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. ProteomicsHome page
J. Li, H. Steen, and S. P. Gygi
Protein Profiling with Cleavable Isotope-coded Affinity Tag (cICAT) Reagents: The Yeast Salinity Stress Response
Mol. Cell. Proteomics, November 1, 2003; 2(11): 1198 - 1204.
[Abstract] [Full Text] [PDF]

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 Toxicol PatholHome page
N. Guerreiro, F. Staedtler, O. Grenet, J. Kehren, and S.-D. Chibout
Toxicogenomics in Drug Development
Toxicol Pathol, August 1, 2003; 31(5): 471 - 479.
[Abstract] [PDF]

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 Mol. Cell. ProteomicsHome page
J. E. Celis, P. Gromov, I. Gromova, J. M. A. Moreira, T. Cabezon, N. Ambartsumian, M. Grigorian, E. Lukanidin, P. thor Straten, P. Guldberg, et al.
Integrating Proteomic and Functional Genomic Technologies in Discovery-driven Translational Breast Cancer Research
Mol. Cell. Proteomics, June 1, 2003; 2(6): 369 - 377.
[Abstract] [Full Text] [PDF]

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 Drug Metab. Dispos.Home page
N. Galeva, D. Yakovlev, Y. Koen, T. Duzhak, and M. Alterman
Direct Identification of Cytochrome P450 Isozymes by Matrix-assisted Laser Desorption/Ionization Time of Flight-Based Proteomic Approach
Drug Metab. Dispos., April 1, 2003; 31(4): 351 - 355.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
K. J. Payne, G. Huang, E. Sahakian, J. Y. Zhu, N. S. Barteneva, L. W. Barsky, M. A. Payne, and G. M. Crooks
Ikaros Isoform X Is Selectively Expressed in Myeloid Differentiation
J. Immunol., March 15, 2003; 170(6): 3091 - 3098.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. ProteomicsHome page
G. Chen, H. Wang, T. G. Gharib, C.-C. Huang, D. G. Thomas, K. A. Shedden, R. Kuick, J. M. G. Taylor, S. L. R. Kardia, D. E. Misek, et al.
Overexpression of Oncoprotein 18 Correlates with Poor Differentiation in Lung Adenocarcinomas
Mol. Cell. Proteomics, February 1, 2003; 2(2): 107 - 116.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. ProteomicsHome page
J. M. Pratt, J. Petty, I. Riba-Garcia, D. H. L. Robertson, S. J. Gaskell, S. G. Oliver, and R. J. Beynon
Dynamics of Protein Turnover, a Missing Dimension in Proteomics
Mol. Cell. Proteomics, August 1, 2002; 1(8): 579 - 591.
[Abstract] [Full Text] [PDF]


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