Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM.

Mol Ther Oncolytics 2019 Sep 22;14:172-178. Epub 2019 May 22.

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Colorectal cancer (CRC) is the third most common cancer worldwide, and liver metastasis presents a major cause of CRC-associated death. Extensive genomic analysis has provided valuable insight into the pathogenesis and progression of CRC; however, a comprehensive proteogenomic characterization of CRC liver metastasis (CLM) has yet to be reported. Here, we analyzed the proteomes of 44 paired normal colorectal tissues and CRC tissues with or without liver metastasis, as well as analyzed genomics of CRC characterized previously by The Cancer Genome Atlas (TCGA) to conduct integrated proteogenomic analyses. We identified a total of 2,170 significantly deregulated proteins associated with CLM, 14.88% of which were involved in metabolic pathways. The mutated peptide number was found to have potential prognosis value, and somatic variants revealed two metabolism-related genes UQCR5 and FDFT1 that frequently mutated only in the liver metastatic cohort and displayed dysregulated protein abundance with biological function and clinical significance in CLM. Proteogenomic characterization and integrative and comparative genomic analysis provides functional context and prognostic value to annotate genomic abnormalities and affords a new paradigm for understanding human colon and rectal cancer liver metastasis.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omto.2019.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579909PMC
September 2019
7 Reads

Publication Analysis

Top Keywords

liver metastasis
16
proteogenomic characterization
8
genomic analysis
8
metabolism-related genes
8
crc
5
liver
5
genome atlas
4
comparative genomic
4
integrative comparative
4
atlas tcga
4
cancer genome
4
tcga conduct
4
proteogenomic analyses
4
significance clm
4
clm proteogenomic
4
integrated proteogenomic
4
characterized cancer
4
conduct integrated
4
characterization integrative
4
genomics crc
4

Similar Publications