Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

Xinxin Peng; Zhongyuan Chen; Farshad Farshidfar; Xiaoyan Xu; Philip L Lorenzi; Yumeng Wang; Feixiong Cheng; Lin Tan; Kamalika Mojumdar; Di Du; Zhongqi Ge; Jun Li; George V Thomas; Kivanc Birsoy; Lingxiang Liu; Huiwen Zhang; Zhongming Zhao; Calena Marchand; John N Weinstein; Oliver F Bathe; Han Liang

doi:10.1016/j.celrep.2018.03.077

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Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

Journal article

Open access

Peer reviewed

Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

Xinxin Peng, Zhongyuan Chen, Farshad Farshidfar, Xiaoyan Xu, Philip L Lorenzi, Yumeng Wang, Feixiong Cheng, Lin Tan, Kamalika Mojumdar, Di Du, …

Cell reports (Cambridge), Vol.23(1), pp.255-269.e4

04/03/2018

DOI: 10.1016/j.celrep.2018.03.077

PMCID: PMC5916795

PMID: 29617665

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https://doi.org/10.1016/j.celrep.2018.03.077View

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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.

Cell Line, Tumor

Core Binding Factor Alpha 2 Subunit - genetics

Core Binding Factor Alpha 2 Subunit - metabolism

Drug Resistance, Neoplasm

HEK293 Cells

Humans

Metabolic Networks and Pathways

Neoplasms - classification

Neoplasms - drug therapy

Neoplasms - metabolism

Snail Family Transcription Factors - genetics

Snail Family Transcription Factors - metabolism

Transcriptome

Details

Title: Subtitle: Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers
Creators: Xinxin Peng - The University of Texas MD Anderson Cancer Center
Zhongyuan Chen - The University of Texas MD Anderson Cancer Center
Farshad Farshidfar - University of Calgary
Xiaoyan Xu - The University of Texas MD Anderson Cancer Center
Philip L Lorenzi - The University of Texas MD Anderson Cancer Center
Yumeng Wang - The University of Texas MD Anderson Cancer Center
Feixiong Cheng - Dana-Farber Cancer Institute
Lin Tan - The University of Texas MD Anderson Cancer Center
Kamalika Mojumdar - The University of Texas MD Anderson Cancer Center
Di Du - The University of Texas MD Anderson Cancer Center
Zhongqi Ge - The University of Texas MD Anderson Cancer Center
Jun Li - The University of Texas MD Anderson Cancer Center
George V Thomas - Oregon Health & Science University
Kivanc Birsoy - Rockefeller University
Lingxiang Liu - Nanjing Medical University
Huiwen Zhang - The University of Texas Health Science Center at Houston
Zhongming Zhao - The University of Texas Health Science Center at Houston
Calena Marchand - University of Waterloo
John N Weinstein - The University of Texas MD Anderson Cancer Center
Oliver F Bathe - University of Calgary
Han Liang - The University of Texas MD Anderson Cancer Center
Contributors: Cancer Genome Atlas Research Network
Deqin Ma (Contributor) - University of Iowa, Pathology
Mohammed M Milhem (Contributor) - University of Iowa, Internal Medicine
Aaron D Bossler (Contributor) - University of Iowa, Pathology
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.23(1), pp.255-269.e4
DOI: 10.1016/j.celrep.2018.03.077
PMID: 29617665
PMCID: PMC5916795
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Grant note: U24 CA143843 / NCI NIH HHS R01 CA169172 / NCI NIH HHS U24 CA210957 / NCI NIH HHS U24 CA209851 / NCI NIH HHS U54 HG003079 / NHGRI NIH HHS P30 CA016672 / NCI NIH HHS U24 CA143883 / NCI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA143799 / NCI NIH HHS R50 CA221675 / NCI NIH HHS U24 CA143867 / NCI NIH HHS U24 CA143858 / NCI NIH HHS U24 CA143882 / NCI NIH HHS U54 HG003067 / NHGRI NIH HHS U24 CA143845 / NCI NIH HHS U24 CA143835 / NCI NIH HHS U54 HG003273 / NHGRI NIH HHS U24 CA143840 / NCI NIH HHS U24 CA144025 / NCI NIH HHS U24 CA210950 / NCI NIH HHS U24 CA143866 / NCI NIH HHS U24 CA210949 / NCI NIH HHS R01 CA175486 / NCI NIH HHS R01 CA163722 / NCI NIH HHS U24 CA143848 / NCI NIH HHS
Language: English
Date published: 04/03/2018
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
Record Identifier: 9984185274602771

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