Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis

被引：69

作者：

Ma, Yu-Shui ^{[1
,2
,3
]}

Huang, Tao ^{[4
]}

Zhong, Xiao-Ming ^{[5
]}

Zhang, Hong-Wei ^{[6
]}

Cong, Xian-Ling ^{[7
]}

Xu, Hong ^{[8
]}

Lu, Gai-Xia ^{[3
]}

Yu, Fei ^{[3
]}

Xue, Shao-Bo ^{[1
]}

Lv, Zhong-Wei ^{[3
]}

Fu, Da ^{[1
]}

机构：

[1] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Cent Lab Med Res, Middle 301 Yanchang Rd, Shanghai 200072, Peoples R China

[2] East China Normal Univ, Coll Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Shanghai 200062, Peoples R China

[3] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Nucl Med, Shanghai 200072, Peoples R China

[4] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai 200025, Peoples R China

[5] Jiangxi Prov Tumor Hosp, Dept Radiol, Nanchang 330029, Jiangxi, Peoples R China

[6] ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Analyt Chem Platforms, Shanghai 201210, Peoples R China

[7] Jilin Univ, China Japan Union Hosp, Tissue Bank, Changchun 130033, Jilin, Peoples R China

[8] Hangzhou Red Cross Hosp, Dept Gastroenterol & Hepatol, Hangzhou 310003, Zhejiang, Peoples R China

来源：

MOLECULAR CANCER | 2018年 / 17卷

基金：

中国国家自然科学基金;

关键词：

CRC; CLM; Proteogenomics; SAAV; Prognosis; STATISTICS;

D O I：

10.1186/s12943-018-0890-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Proteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value. Methods: Here, 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. Results: We 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 (DMRTB1(R202H) and PARP4(V4581)) 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. Conclusions: Our proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis.

引用

页数：14

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