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A Pilot Proteogenomic Study with Data Integration Identifies MCT1 and GLUT1 as Prognostic Markers in Lung Adenocarcinoma

机译:数据集成的初步蛋白质组学研究确定了MCT1和GLUT1是肺腺癌的预后标志物

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摘要

We performed a pilot proteogenomic study to compare lung adenocarcinoma to lung squamous cell carcinoma using quantitative proteomics (6-plex TMT) combined with a customized Affymetrix GeneChip. Using MaxQuant software, we identified 51,001 unique peptides that mapped to 7,241 unique proteins and from these identified 6,373 genes with matching protein expression for further analysis. We found a minor correlation between gene expression and protein expression; both datasets were able to independently recapitulate known differences between the adenocarcinoma and squamous cell carcinoma subtypes. We found 565 proteins and 629 genes to be differentially expressed between adenocarcinoma and squamous cell carcinoma, with 113 of these consistently differentially expressed at both the gene and protein levels. We then compared our results to published adenocarcinoma versus squamous cell carcinoma proteomic data that we also processed with MaxQuant. We selected two proteins consistently overexpressed in squamous cell carcinoma in all studies, MCT1 (SLC16A1) and GLUT1 (SLC2A1), for further investigation. We found differential expression of these same proteins at the gene level in our study as well as in other public gene expression datasets. These findings combined with survival analysis of public datasets suggest that MCT1 and GLUT1 may be potential prognostic markers in adenocarcinoma and druggable targets in squamous cell carcinoma. Data are available via ProteomeXchange with identifier PXD002622.
机译:我们进行了一项蛋白质组学试验研究,使用定量蛋白质组学(6-plex TMT)结合定制的Affymetrix GeneChip将肺腺癌与肺鳞状细胞癌进行比较。使用MaxQuant软件,我们鉴定了51,001个独特的肽,它们映射到7,241个独特的蛋白质,并从这些鉴定出的6,373个基因与匹配的蛋白质表达中进行了进一步的分析。我们发现基因表达和蛋白质表达之间存在较小的相关性。这两个数据集都能够独立概括腺癌和鳞状细胞癌亚型之间的已知差异。我们发现在腺癌和鳞状细胞癌之间有565种蛋白质和629个基因差异表达,其中113个在基因和蛋白质水平上均差异表达。然后,我们将我们的结果与已发表的腺癌和鳞状细胞癌蛋白质组学数据进行了比较,这些数据也用MaxQuant处理。在所有研究中,我们选择了在鳞状细胞癌中始终过度表达的两种蛋白质,MCT1(SLC16A1)和GLUT1(SLC2A1),以进行进一步研究。在我们的研究以及其他公共基因表达数据集中,我们在基因水平上发现了这些相同蛋白质的差异表达。这些发现与公共数据集的生存分析相结合,表明MCT1和GLUT1可能是腺癌的潜在预后标志物,是鳞状细胞癌的可靶向药物。数据可通过ProteomeXchange获得,其标识符为PXD002622。

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