期刊
MOLECULAR CANCER
卷 17, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12943-018-0890-1
关键词
CRC; CLM; Proteogenomics; SAAV; Prognosis
资金
- National Natural Science Foundation of China [81772932, 81472202, 81201535, 81302065, 81702243]
- Fundamental Research Funds for the Central Universities [22120170212, 22120170117]
- Shanghai Natural Science Foundation [12ZR1436000]
- Program of Shanghai Academic/Technology Research Leader [18XD1403000]
- Shanghai Municipal Commission of Health and Family Planning [201540228]
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.
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