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Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers
Xinxin Peng, Zhongyuan Chen, Farshad Farshidfar, Xu Xiaoyan, Philip L. Lorenzi, Yumeng Wang, Feixiong Cheng, Lin Tan, Kamalika Mojumdar, Di Du, Zhongqi Ge, George Thomas, Kıvanç Birsoy, Lingxiang Liu, Huiwen Zhang, Zhongming Zhao, Calena R. Marchand, John N. Weinstein, Rory Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Liming Yang, Jean C. Zenklusen, Jiashan Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy Defreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Michael S. Lawrence, Pei Lin, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila M. Reynolds, Ilya Shmulevich, Vésteinn Thórsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael P. Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Galen F. Gao, Benjamin Groß, Zachary Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah Phillips, Ed Reznik, Francisco Sánchez-Vega, Chris Sander, Nikolaus Schultz, Robert P. Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul T. Spellman, Christopher C. Benz, Joshua M. Stuart, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey Gabriel, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju Kucherlapati, Stephen B. Baylin, Leslie Cope, Ludmila Danilova, Phillip H. Lai, Dennis T. Maglinte, David Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Katherine A. Hoadley, Alan P. Hoyle, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Peter W. Laird, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle R. Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Hai Hu, Viktoriya Korchina, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna M. Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Xi Liu, Fengmei Zhao, Julian M. Hess, Elizabeth L. Appelbaum, Matthew H. Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark E. Sherman, Eric N. Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall M. Corcoran, Tony Costello, Christopher M. Hovens, André Lopes Carvalho, Ana Carolina de Carvalho, José Humberto Tavares Guerreiro Fregnani, Adhemar Longatto‐Filho, Rui Manuel Reis, Cristovam Scapulatempo‐Neto, Henrique C.S. Silveira, Daniel Onofre Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Shabunin Av, Mikhail Tavobilov, Christopher McPherson, Ronald E. Warnick, Ross S. Berkowitz, Daniel Cramer, Colleen M. Feltmate, Neil S. Horowitz, Adam S. Kibel, Michael G. Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz‐Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino Maria De Rose, Felice Giuliante, Marc T. Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Leonid Kvecher, Caroline Larson, Richard Mural, Stella Somiari, Aleš Vícha, Tomáš Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John A. Chabot, Hanina Hibshoosh, Antonia R. Sepulveda, Tao Su, Timothy C. Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman‐Roman, Xavier Sastre, Marc‐Henri Stern, Sabina Signoretti, Andrew Berchuck, Darell D. Bigner, Eric Lipp, Jeffrey S. Marks, Shannon J. McCall, Roger E. McLendon, Angeles Alvarez Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith A. Delman, Seth Force, Fadlo R. Khuri, Kelly R. Magliocca, Shishir K. Maithel, Jeffrey J. Olson, Taofeek K. Owonikoko, Alan Pickens, Suresh S. Ramalingam, Dong Min Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert H. J. Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, J. C. Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Robert Stoehr, Helge Täubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Maciej Wiznerowicz, Ki Wha Chung, W. Jeffrey Edenfield, Julie Martin, Éric Baudin, Glenn J. Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven N. Kalkanis, Tom Mikkelsen, Houtan Noushmehr, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elı́as Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bùi Đức Phú, Yufang Tang, Howard Colman, Kimberley Evason, Peter Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave S.�B. Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh J. Borad, Alan H. Bryce, Erik P. Castle, Vishal S. Chandan, John C. Cheville, John A. Copland, Michael B. Farnell, Thomas J. Flotte, Nasra H. Giama, Thai H. Ho, Michael L. Kendrick, Jean‐Pierre Kocher, Karla Kopp, Catherine D. Moser, David M. Nagorney, Daniel R. O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria M. Petersen, Florencia G. Que, Michael Rivera, Lewis R. Roberts, Robert C. Smallridge, Thomas C. Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Charles C. Guo, Alexander J. Lazar, Christopher J. Logothetis, Funda Meric‐Bernstam, César A. Moran, Lois M. Ramondetta, David C. Rice, Anil K. Sood, Pheroze Tamboli, Timothy C. Thompson, Patricia Troncoso, Anne S. Tsao, Ignacio Wistuba, Candace Carter, Lauren E. Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina V. Long, Graham J. Mann, Michael C. Quinn, Robyn P.M. Saw, Richard A. Scolyer, Kerwin F. Shannon, Andrew J. Spillane, Jonathan R. Stretch, Maria Synott, John R. Thompson, James S. Wilmott, Hikmat Al‐Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor E. Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Jennifer R. Smith, Howard Zaren, Joong‐Won Park, Nguyễn Phi Hùng, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacák, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey I. Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John G. Bartlett, Jay Engel, Sébastien Gilbert, Jeremy Parfitt, Harman Sekhon, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter J. Urba, Nicholas K. Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gian Luca Grazi, Mirella Marino, Roberta Merola, Ronald R. de Krijger, Anne‐Paule Gimenez‐Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Gene H. Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel P. Raymond, Cathy Schilero, Kathy Smolenski, Quaid Morris, Jeffrey A. Borgia, Mark Pool, Christopher W. Seder, Kerstin Junker, Larsson Omberg, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl‐Friedrich Becker, Klaus‐Peter Janssen, Julia Slotta‐Huspenina, Mohamed H. Abdel‐Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James C. Lang, Norman L. Lehman, Randy Mandt, Phuong L. Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul E. Wakely, Paul Hansen, Ronald M. Lechan, James Powers, Arthur S. Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima P. Porten, Jens Waldmann, Martin Faßnacht, L. Sylvia, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark A. Nelson, Oliver F. Bathe, Peter R. Carroll, June M. Chan, Philip J. DiSaia, Pat Glenn, Robin Kate Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith‐McCune, Scott Vandenberg, Kevin K. Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis A. Carey, Ian Forgie, Massimo Mannelli, Michael E. Carney, Brenda Hernandez, Benito Campos, Christel Herold‐Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Andrew K. Godwin, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David G. Beer, Thomas J. Giordano, Anne‐Marie Mes‐Masson, Fred Saad, Thèrése Bocklage, Lisa M. Landrum, Robert S. Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary E. Zuna, Michaël Feldman, Federico Valdivieso, Rajiv Dhir, James D. Luketich, Edna M. Mora Pinero, Mario Quintero-Aguilo, Carlos Gilberto Carlotti, José Sebastião dos Santos, Rafael Kemp, Ajith Sankarankuty, Daniela Pretti da Cunha Tirapelli, James W.F. Catto, Kathy Agnew, Elizabeth M. Swisher, Jenette Creaney, B. W. Robinson, Carl Simon Shelley, Eryn M. Godwin, Sara Kendall, Cassaundra Shipman, Carol R. Bradford, Thomas E. Carey, Jeffey Moyer, Lisa A. Peterson, Mark E. Prince, Laura S. Rozek, Gregory T. Wolf, Rayleen Bowman, Kwun M. Fong, Ian A. Yang, Robert J. Korst, W. Kimryn Rathmell, J. Leigh Fantacone-Campbell, Jeffrey A. Hooke, Albert J. Kovatich, Craig D. Shriver, John F. DiPersio, Bettina F. Drake, Ramaswamy Govindan, Sharon E. Heath, Timothy J. Ley, Brian A. Van Tine, Peter Westervelt, Mark A. Rubin, Jung Il Lee, Natália D. Aredes, Armaz Mariamidze
Bibliographic record
VenueCell Reports · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Hypoxia, and Metabolism
Canadian institutionsUniversity of WaterlooUniversity of Calgary
FundersNational Human Genome Research InstituteInvitaeAstex PharmaceuticalsNational Cancer InstituteNational Institutes of HealthBoston Scientific CorporationArray BioPharmaUniversity of Texas SystemUniversity of Texas MD Anderson Cancer CenterCancer Prevention and Research Institute of TexasNational Institute on Deafness and Other Communication DisordersBristol-Myers Squibb
KeywordsComputational biologyBiologyGene expressionClinical significanceRelevance (law)CancerCancer researchGene expression profilingGeneGeneticsBioinformaticsMedicineInternal medicine
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.010
GPT teacher head0.282
Teacher spread0.272 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations393
Published2018
Admission routes1
Has abstractyes