TY - JOUR
T1 - Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers
AU - The Cancer Genome Atlas Research Network
AU - Peng, Xinxin
AU - Chen, Zhongyuan
AU - Farshidfar, Farshad
AU - Xu, Xiaoyan
AU - Lorenzi, Philip L.
AU - Tan, Lin
AU - Mojumdar, Kamalika
AU - Ge, Zhongqi
AU - Weinstein, John N.
AU - Liu, Yuexin
AU - Zhang, Wei
AU - Akbani, Rehan
AU - Broom, Bradley M.
AU - Ju, Zhenlin
AU - Kanchi, Rupa Sridevi
AU - Korkut, Anil
AU - Li, Jun
AU - Ling, Shiyun
AU - Liu, Wenbin
AU - Lu, Yiling
AU - Mills, Gordon B
AU - Uppore Kukkillaya, Arvind Rao
AU - Zhang, Jiexin
AU - Liu, Xiuping
AU - Wang, Linghua
AU - Fregnani, José Humberto T. G.
AU - Reis, Rui M. V.
AU - Ajani, Jaffer A.
AU - Behrens, Carmen
AU - Bondaruk, Jolanta
AU - Broaddus, Russell
AU - Czerniak, Bogdan
AU - Esmaeli, Bita
AU - Fujimoto, Junya
AU - Gershenwald, Jeffrey
AU - Guo, Charles
AU - Lazar, Alexander J.
AU - Logothetis, Christopher
AU - Meric-Bernstam, Funda
AU - Moran, Cesar
AU - Ramondetta, Lois
AU - Rice, David
AU - Sood, Anil
AU - Tamboli, Pheroze
AU - Thompson, Timothy
AU - Troncoso, Patricia
AU - Tsao, Anne
AU - Wistuba, Ignacio
AU - von Deimling, Andreas
AU - Liang, Han
N1 - Publisher Copyright:
© 2018 The Author(s)
PY - 2018/4/3
Y1 - 2018/4/3
N2 - 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. Peng et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to characterize tumor subtypes based on the expression of seven metabolic pathways. They find metabolic expression subtypes are associated with patient survivals and suggest the therapeutic and predictive relevance of subtype-related master regulators.
AB - 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. Peng et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to characterize tumor subtypes based on the expression of seven metabolic pathways. They find metabolic expression subtypes are associated with patient survivals and suggest the therapeutic and predictive relevance of subtype-related master regulators.
KW - The Cancer Genome Atlas
KW - carbohydrate metabolism
KW - drug sensitivity
KW - master regulator
KW - prognostic markers
KW - somatic drivers
KW - therapeutic targets
KW - tumor subtypes
UR - http://www.scopus.com/inward/record.url?scp=85044606356&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044606356&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.03.077
DO - 10.1016/j.celrep.2018.03.077
M3 - Article
C2 - 29617665
AN - SCOPUS:85044606356
SN - 2211-1247
VL - 23
SP - 255-269.e4
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -