Discordant protein and mRNA expression in lung adenocarcinomas
Discordant protein and mRNA expression in lung adenocarcinomas
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DOI：
10.1074/mcp.m200008-mcp200
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发表时间：
2002-04-01
影响因子：
7
通讯作者：
Beer, DG
中科院分区：
文献类型：
--
作者：
Chen, GA;Gharib, TG;Beer, DG
在mRNA水平上测得的基因表达与相应的蛋白质水平之间的关系在人类癌症中没有很好地表征。在这项研究中，我们比较了同一肺腺癌中一组基因的mRNA和蛋白表达。使用二维聚丙烯酰胺凝胶电泳分析了76个肺腺癌和9个非肿瘤肺组织的165个蛋白质斑点的丰度。使用基质辅助激光解吸/电离质谱法鉴定了特异性多肽。对于相同的85个样品，使用寡核苷酸微阵列确定mRNA水平，从而可以对165个蛋白质斑点中的mRNA和蛋白质表达进行比较分析。 165个蛋白质斑点（17％）或98个基因中的21个（21.4％）中有28个具有统计学意义的蛋白质和mRNA表达（r> 0.2445; p <0.05）具有统计学意义的相关性；但是，在所有165种蛋白中，相关系数值（R）范围为-0.467至0.442。相关系数值与蛋白质丰度无关。此外，如果在165个蛋白质斑点（98个基因）中应用所有样品中的mRNA或蛋白质平均水平，则mRNA和蛋白表达之间没有明显的相关性（r = -0.025）。具有多种同工型的蛋白质之间的mRNA/蛋白质相关系数也有所不同，表明潜在的分开的同工型特异性机制来调节蛋白质丰度。在mRNA和蛋白质之间具有显着相关性的21个基因中，I期和III期肺腺癌之间的5个基因显着差异。使用对同一肺腺癌中mRNA和蛋白表达的定量分析，我们表明，只有一部分蛋白质与mRNA丰度显示出显着的相关性。
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.