Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis.
Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis.
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人结直肠癌肝转移的蛋白质组学表征和综合整合基因组分析
DOI：
10.1186/s12943-018-0890-1
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发表时间：
2018-09-21
期刊：
影响因子：
37.3
通讯作者：
Fu D
中科院分区：
文献类型：
--
作者：
Ma YS;Huang T;Zhong XM;Zhang HW;Cong XL;Xu H;Lu GX;Yu F;Xue SB;Lv ZW;Fu D
BackgroundProteogenomiccharacterization和整合和比较基因组学分析提供了一个功能的背景下，注释基因组异常与预后value.MethodsHere，我们分析了蛋白质组，并进行了全外显子组和转录组测序和单核苷酸多态性阵列分析的2套三联体样品组成的正常结直肠组织，原发性CRC组织，结果共鉴定出112个CNV-mRNA-蛋白相关分子，包括上调表达的与预后相关的COL 1A 2和BGN，以及4个最强热点（染色体X、7、16和1）驱动CRC肝转移中的总体mRNA丰度变化。两个位点（DMRTB 1 R202和PARP 4V 458 I）仅在肝转移队列中频繁突变，并显示出失调的蛋白质丰度。此外，我们证实，突变的肽数具有潜在的预后价值和体细胞变异显示增加的蛋白丰度，包括高MYH 9和CCT 6A的表达，与clinical significant.ConclusionsOur蛋白基因组学特征和整合和比较基因组学分析提供了一个新的范例，为了解人类结肠癌和直肠癌肝transfer.Trial registrationClinicalTrials，NCT 02917707。于2016年9月28日注册， https://clinicaltrials.gov/ct2/show/NCT02917707 .
BackgroundProteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value.MethodsHere, we analyzed the proteomes and performed whole exome and transcriptome sequencing and single nucleotide polymorphism array profiling for 2 sets of triplet samples comprised of normal colorectal tissue, primary CRC tissue, and synchronous matched liver metastatic tissue.ResultsWe identified 112 CNV-mRNA-protein correlated molecules, including up-regulated COL1A2 and BGN associated with prognosis, and four strongest hot spots (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver metastasis. Two sites (DMRTB1R202Hand PARP4V458I) were revealed to frequent mutate only in the liver metastatic cohort and displayed dysregulated protein abundance. Moreover, we confirmed that the mutated peptide number has potential prognosis value and somatic variants displayed increased protein abundance, including high MYH9 and CCT6A expression, with clinical significance.ConclusionsOur proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis.Trial registrationClinicalTrials, NCT02917707. Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707 .
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