13
IRUS Total
Downloads
  Altmetric

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers

File Description SizeFormat 
1-s2.0-S2211124718304388-main.pdfPublished version3.75 MBAdobe PDFView/Open
Title: Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers
Authors: 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
Bathe, OF
Liang, H
Item Type: Journal Article
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.
Issue Date: 3-Apr-2018
Date of Acceptance: 19-Mar-2018
URI: http://hdl.handle.net/10044/1/71259
DOI: https://doi.org/10.1016/j.celrep.2018.03.077
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 255
End Page: 269
Journal / Book Title: Cell Reports
Volume: 23
Issue: 1
Copyright Statement: © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
HETEROGENEITY
MICRORNAS
HALLMARKS
PATTERNS
SURVIVAL
GLIOMA
ATLAS
MYC
The Cancer Genome Atlas
carbohydrate metabolism
drug sensitivity
master regulator
prognostic markers
somatic drivers
therapeutic targets
tumor subtypes
Cancer Genome Atlas Research Network
Science & Technology
Life Sciences & Biomedicine
Cell Biology
HETEROGENEITY
MICRORNAS
HALLMARKS
PATTERNS
SURVIVAL
GLIOMA
ATLAS
MYC
Publication Status: Published
Online Publication Date: 2018-04-05
Appears in Collections:Department of Surgery and Cancer