AI Article Synopsis

  • The study combines proteomic and genomic analyses to explore colorectal cancer (CRC) and its metastasis to the liver.
  • It identifies 112 molecular markers correlated with gene and protein expression that may indicate prognosis, including specific genes associated with liver metastasis.
  • Findings suggest a new approach to understanding CRC and provide insights into mutations and protein abundance linked to clinical outcomes.

Article Abstract

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 and PARP4) 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.

Trial Registration: ClinicalTrials, NCT02917707. Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707 .

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148962PMC
http://dx.doi.org/10.1186/s12943-018-0890-1DOI Listing

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