Proteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures Journal Article

   

Authors:	Tanaka, A.; Ogawa, M.; Zhou, Y.; Namba, K.; Hendrickson, R. C.; Miele, M. M.; Li, Z.; Klimstra, D. S.; Buckley, P. G.; Gulcher, J.; Wang, J. Y.; Roehrl, M. H. A.
Article Title:	Proteogenomic characterization of primary colorectal cancer and metastatic progression identifies proteome-based subtypes and signatures
Abstract:	Metastatic progression of colorectal adenocarcinoma (CRC) remains poorly understood and poses significant challenges for treatment. To overcome these challenges, we performed multiomics analyses of primary CRC and liver metastases. Genomic alterations, such as structural variants or copy number alterations, were enriched in oncogenes and tumor suppressor genes and increased in metastases. Unsupervised mass spectrometry-based proteomics of 135 primary and 123 metastatic CRCs uncovered distinct proteomic subtypes, three each for primary and metastatic CRCs, respectively. Integrated analyses revealed that hypoxia, stemness, and immune signatures characterize these 6 subtypes. Hypoxic CRC harbors high epithelial-to-mesenchymal transition features and metabolic adaptation. CRC with a stemness signature shows high oncogenic pathway activation and alternative telomere lengthening (ALT) phenotype, especially in metastatic lesions. Tumor microenvironment analysis shows immune evasion via modulation of major histocompatibility complex (MHC) class I/II and antigen processing pathways. This study characterizes both primary and metastatic CRCs and provides a large proteogenomics dataset of metastatic progression. © 2024
Keywords:	colorectal cancer; mass spectrometry; biomarkers; metastasis; proteomics; hypoxia; molecular signature; stemness; subtyping; tumor immune microenvironment; cp: cancer
Journal Title:	Cell Reports
Volume:	43
Issue:	2
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2024-02-27
Start Page:	113810
Language:	English
DOI:	10.1016/j.celrep.2024.113810
PROVIDER:	scopus
PUBMED:	38377004
PMCID:	PMC11288375
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185606213&doi=10.1016%2fj.celrep.2024.113810&partnerID=40&md5=784f16cc16a7c6284e75bbb2a75af62c
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/213829