Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers
01 Pubblicazione su rivista
Peng Xinxin, Chen Zhongyuan, Farshidfar Farshad, Xu Xiaoyan, Lorenzi Philip L., Wang Yumeng, Cheng Feixiong, Tan Lin, Mojumdar Kamalika, Du Di, Ge Zhongqi, Li Jun, Thomas George V., Birsoy Kivanc, Liu Lingxiang, Zhang Huiwen, Zhao Zhongming, Marchand Calena, Weinstein John N., Caesar-Johnson Samantha J., Demchok John A., Felau Ina, Kasapi Melpomeni, Ferguson Martin L., Hutter Carolyn M., Sofia Heidi J., Tarnuzzer Roy, Wang Zhining, Yang Liming, Zenklusen Jean C., Zhang Jiashan (Julia), Chudamani Sudha, Liu Jia, Lolla Laxmi, Naresh Rashi, Pihl Todd, Sun Qiang, Wan Yunhu, Wu Ye, Cho Juok, Defreitas Timothy, Frazer Scott, Gehlenborg Nils, Getz Gad, Heiman David I., Kim Jaegil, Lawrence Michael S., Lin Pei, Meier Sam, Noble Michael S., Saksena Gordon, Voet Doug, Zhang Hailei, Bernard Brady, Chambwe Nyasha, Dhankani Varsha, Knijnenburg Theo, Kramer Roger, Leinonen Kalle, Liu Yuexin, Miller Michael, Reynolds Sheila, Shmulevich Ilya, Thorsson Vesteinn, Zhang Wei, Akbani Rehan, Broom Bradley M., Hegde Apurva M., Ju Zhenlin, Kanchi Rupa S., Korkut Anil, Li Jun, Liang Han, Ling Shiyun, Liu Wenbin, Lu Yiling, Mills Gordon B., Ng Kwok-Shing, Rao Arvind, Ryan Michael, Wang Jing, Weinstein John N., Zhang Jiexin, Abeshouse Adam, Armenia Joshua, Chakravarty Debyani, Chatila Walid K., de Bruijn Ino, Gao Jianjiong, Gross Benjamin E., Heins Zachary J., Kundra Ritika, La Konnor, Ladanyi Marc, Luna Augustin, Nissan Moriah G., Ochoa Angelica, Phillips Sarah M., Reznik Ed, Sanchez-Vega Francisco, Sander Chris, Schultz Nikolaus, Sheridan Robert, Sumer S. Onur, Sun Yichao, Taylor Barry S., Wang Jioajiao, Zhang Hongxin, Anur Pavana, Peto Myron, Spellman Paul, Benz Christopher, Stuart Joshua M., Wong Christopher K., Yau Christina, Hayes D. Neil, Parker Joel S., Wilkerson Matthew D., Ally Adrian, Balasundaram Miruna, Bowlby Reanne, Brooks Denise, Carlsen Rebecca, Chuah Eric, Dhalla Noreen, Holt Robert, Jones Steven J. M., Kasaian Katayoon, Lee Darlene, Ma Yussanne, Marra Marco A., Mayo Michael, Moore Richard A., Mungall Andrew J., Mungall Karen, Robertson A. Gordon, Sadeghi Sara, Schein Jacqueline E., Sipahimalani Payal, Tam Angela, Thiessen Nina, Tse Kane, Wong Tina, Berger Ashton C., Beroukhim Rameen, Cherniack Andrew D., Cibulskis Carrie, Gabriel Stacey B., Gao Galen F., Ha Gavin, Meyerson Matthew, Schumacher Steven E., Shih Juliann, Kucherlapati Melanie H., Kucherlapati Raju S., Baylin Stephen, Cope Leslie, Danilova Ludmila, Bootwalla Moiz S., Lai Phillip H., Maglinte Dennis T., Van Den Berg David J., Weisenberger Daniel J., Auman J. Todd, Balu Saianand, Bodenheimer Tom, Fan Cheng, Hoadley Katherine A., Hoyle Alan P., Jefferys Stuart R., Jones Corbin D., Meng Shaowu, Mieczkowski Piotr A., Mose Lisle E., Perou Amy H., Perou Charles M., Roach Jeffrey, Shi Yan, Simons Janae V., Skelly Tara, Soloway Matthew G., Tan Donghui, Veluvolu Umadevi, Fan Huihui, Hinoue Toshinori, Laird Peter W., Shen Hui, Zhou Wanding, Bellair Michelle, Chang Kyle, Covington Kyle, Creighton Chad J., Dinh Huyen, Doddapaneni Harshavardhan, Donehower Lawrence A., Drummond Jennifer, Gibbs Richard A., Glenn Robert, Hale Walker, Han Yi, Hu Jianhong, Korchina Viktoriya, Lee Sandra, Lewis Lora, Li Wei, Liu Xiuping, Morgan Margaret, Morton Donna, Muzny Donna, Santibanez Jireh, Sheth Margi, Shinbrot Eve, Wang Linghua, Wang Min, Wheeler David A., Xi Liu, Zhao Fengmei, Hess Julian, Appelbaum Elizabeth L., Bailey Matthew, Cordes Matthew G., Ding Li, Fronick Catrina C., Fulton Lucinda A., Fulton Robert S., Kandoth Cyriac, Mardis Elaine R., Mclellan Michael D., Miller Christopher A., Schmidt Heather K., Wilson Richard K., Crain Daniel, Curley Erin, Gardner Johanna, Lau Kevin, Mallery David, Morris Scott, Paulauskis Joseph, Penny Robert, Shelton Candace, Shelt
ISSN: 2211-1247
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
