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Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers. Cell Rep 2018 Apr 03;23(1):255-269.e4

Date

04/05/2018

Pubmed ID

29617665

Pubmed Central ID

PMC5916795

DOI

10.1016/j.celrep.2018.03.077

Scopus ID

2-s2.0-85044606356 (requires institutional sign-in at Scopus site)   171 Citations

Abstract

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1-master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility.

Author List

Peng X, Chen Z, Farshidfar F, Xu X, Lorenzi PL, Wang Y, Cheng F, Tan L, Mojumdar K, Du D, Ge Z, Li J, Thomas GV, Birsoy K, Liu L, Zhang H, Zhao Z, Marchand C, Weinstein JN, Cancer Genome Atlas Research Network, Bathe OF, Liang H

Author

Zhongyuan Chen PhD Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Line, Tumor
Core Binding Factor Alpha 2 Subunit
Drug Resistance, Neoplasm
HEK293 Cells
Humans
Metabolic Networks and Pathways
Neoplasms
Snail Family Transcription Factors
Transcriptome