Proteogenomic Study beyond Chromosome 9: New Insight into Expressed Variant Proteome and Transcriptome in Human Lung Adenocarcinoma Tissues
Proteogenomic Study beyond Chromosome 9: New Insight into Expressed Variant Proteome and Transcriptome in Human Lung Adenocarcinoma Tissues
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DOI：
10.1021/acs.jproteome.5b00544
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发表时间：
2015-12-01
影响因子：
4.4
通讯作者：
Cho, Je-Yoel
中科院分区：
文献类型：
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作者：
Kim, Yong-In;Lee, Jongan;Cho, Je-Yoel
这是一个与9号染色体（Chr 9）相关的人类蛋白质组计划（HPP）的报告。为了揭示蛋白质组中缺失的蛋白质和未发现的特征，对五对肺腺癌肿瘤和相邻非肿瘤组织进行了LC-MS/MS分析和基于下一代RNA测序（RNA-seq）的鉴定和表征。在我们之前的染色体中心人类蛋白质组计划（C-HPP）特刊之前，Chr 9上还有170个剩余的缺失蛋白质（neXtProt 2013.09.26 rel.）;目前仍有133个（neXtProt 2015.04.28 rel.）。在蛋白质组学研究中，我们发现了两个需要后续工作的缺失蛋白质候选物，以及一个未发现的蛋白质。RNA-seq分析检测了所有五种肿瘤组织中四种非同义（NS）单核苷酸多态性（SNP）（CDH 17，HIST 1H 1 T，SAPCD 2和ZNF 695）和三种同义SNP（CDH 17，CST 1和HNF 1A）的RNA表达，但未在任何相邻正常组织中检测到。通过基于个体RNA-seq数据构建癌症患者样本特异性蛋白质数据库，并通过搜索来自同一样本的蛋白质组学数据，我们在四个基因（LTF、HDLBP、TF和HBD）中鉴定出四个错义突变。其中两个突变在肿瘤样本中发现，但在配对的正常组织中没有发现。总之，我们对人类原发性肺肿瘤组织的蛋白基因组学研究检测到了额外的错义突变，并揭示了新的错义突变和同义SNP特征，其中一些是肺癌特有的。来自质谱分析的数据已保存在ProteomeXchange中，标识符为PXD 002523。
This is a report of a human proteome project (HPP) related to chromosome 9 (Chr 9). To reveal missing proteins and undiscovered features in proteogenomes, both LC-MS/MS analysis and next-generation RNA sequencing (RNA-seq)-based identification and characterization were conducted on five pairs of lung adenocarcinoma tumors and adjacent nontumor tissues. Before our previous Chromosome-Centric Human Proteome Project (C-HPP) special issue, there were 170 remaining missing proteins on Chr 9 (neXtProt 2013.09.26 rel.); 133 remain at present (neXtProt 2015.04.28 rel.). In the proteomics study, we found two missing protein candidates that require follow-up work and one unrevealed protein across all chromosomes. RNA-seq analysis detected RNA expression for four nonsynonymous (NS) single nucleotide polymorphisms (SNPs) (in CDH17, HIST1H1T, SAPCD2, and ZNF695) and three synonymous SNPs (in CDH17, CST1, and HNF1A) in all five tumor tissues but not in any of the adjacent normal tissues. By constructing a cancer patient sample-specific protein database based on individual RNA-seq data and by searching the proteomics data from the same sample, we identified four missense mutations in four genes (LTF, HDLBP, TF, and HBD). Two of these mutations were found in tumor samples but not in paired normal tissues. In summary, our proteogenomic study of human primary lung tumor tissues detected additional and revealed novel missense mutations and synonymous SNP signatures, some of which are specific to lung cancers. Data from mass spectrometry have been deposited in the ProteomeXchange with the identifier PXD002523.