Discordant Protein and mRNA Expression in Lung Adenocarcinomas *

By Guoan Chen, Tarek G Gharib, Chiang-Ching Huang, Jeremy M. G. Taylor, David E. Misek, S. Kardia, T. Giordano, M. Iannettoni, M. Orringer, S. Hanash and 1 more. Molecular & Cellular Proteomics, 2002

968 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0fe3843ce2b9d5a9afb552fd9910aeb320777f6f

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Citations in the corpus

• Comparing protein abundance and mRNA expression levels on a genomic scale (2003, neutral): “An additional cancer study [26] showed a co m m nt”
• From big data analysis to personalized medicine for all: challenges and opportunities (2015, background): “No high correlations between the two domains were observed as reported by multiple studies, and this was attributed to post-transcriptional and posttranslational regulations [96–99].”
• Proteomic analysis of soybean [Glycine max (L.) Meer.] seeds during imbibition at chilling temperature (2010, background): “Level of mRNA may not always correlate well with the level of its protein, the key player in the cell (Chen et al. 2002).”
• Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes (2012, background): “First, protein levels are known to not always correlate well with mRNA levels [50,51].”
• Integrated Genomic and Proteomic Analyses of Gene Expression in Mammalian Cells*S (2004, background): “Discordant expression of protein and mRNA was also observed in lung adenocarcinomas (6).”