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

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art_PENG_Molecular_Characterization_and_Clinical_Relevance_of_Metabolic_Expression_2018.PDF (4.39 MB)
Citações na Scopus
186
Tipo de produção
article
Data de publicação
2018
Editora
CELL PRESS
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
PENG, Xinxin
CHEN, Zhongyuan
FARSHIDFAR, Farshad
XU, Xiaoyan
LORENZI, Philip L.
WANG, Yumeng
CHENG, Feixiong
TAN, Lin
MOJUMDAR, Kamalika
DU, Di
Autor de Grupo de pesquisa
Canc Genome Atlas Res Network
Editores
Coordenadores
Organizadores
Citação
CELL REPORTS, v.23, n.1, p.255-269.e4, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 subtypesmodulates 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.
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URI
https://observatorio.fm.usp.br/handle/OPI/30117
Referências
  1. Aytes A, 2014, CANCER CELL, V25, P638, DOI 10.1016/j.ccr.2014.03.017
  2. Barretina J, 2012, NATURE, V483, P603, DOI 10.1038/nature11003
  3. Chan B, 2015, CANCER LETT, V356, P301, DOI 10.1016/j.canlet.2014.10.011
  4. Claus EB, 2015, NEUROSURG FOCUS, V38, DOI 10.3171/2014.10.FOCUS12367
  5. Dang L, 2009, NATURE, V462, P739, DOI 10.1038/nature08617
  6. DeBerardinis RJ, 2016, SCI ADV, V2, DOI 10.1126/sciadv.1600200
  7. Eckel-Passow JE, 2015, NEW ENGL J MED, V372, P2499, DOI 10.1056/NEJMoa1407279
  8. Fabregat A, 2016, NUCLEIC ACIDS RES, V44, pD481, DOI 10.1093/nar/gkv1351
  9. Gaude E, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms13041
  10. Haider S, 2016, GENOME BIOL, V17, DOI 10.1186/s13059-016-0999-8
  11. Hakimi AA, 2016, CANCER CELL, V29, P104, DOI 10.1016/j.ccell.2015.12.004
  12. Hanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013
  13. Haverty PM, 2016, NATURE, V533, P333, DOI 10.1038/nature17987
  14. Hay N, 2016, NAT REV CANCER, V16, P635, DOI 10.1038/nrc.2016.77
  15. Heiden MGV, 2009, SCIENCE, V324, P1029, DOI 10.1126/science.1160809
  16. Hu J, 2013, NAT BIOTECHNOL, V31, P522, DOI 10.1038/nbt.2530
  17. Iorio F, 2016, CELL, V166, P740, DOI 10.1016/j.cell.2016.06.017
  18. Kim J, 2017, NATURE, V541, P169, DOI 10.1038/nature20805
  19. Kruiswijk F, 2015, NAT REV MOL CELL BIO, V16, P393, DOI 10.1038/nrm4007
  20. Lachmann A, 2016, BIOINFORMATICS, V32, P2233, DOI 10.1093/bioinformatics/btw216
  21. Lawrence MS, 2013, NATURE, V499, P214, DOI 10.1038/nature12213
  22. Lefebvre C, 2010, MOL SYST BIOL, V6, DOI 10.1038/msb.2010.31
  23. Mermel CH, 2011, GENOME BIOL, V12, DOI 10.1186/gb-2011-12-4-r41
  24. Mootha VK, 2003, NAT GENET, V34, P267, DOI 10.1038/ng1180
  25. Nilsson R, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms4128
  26. Pavlova NN, 2016, CELL METAB, V23, P27, DOI 10.1016/j.cmet.2015.12.006
  27. Reznik E, 2015, PLOS COMPUT BIOL, V11, DOI 10.1371/journal.pcbi.1004176
  28. Rottiers V, 2012, NAT REV MOL CELL BIO, V13, P239, DOI 10.1038/nrm3313
  29. Shannon P, 2003, GENOME RES, V13, P2498, DOI 10.1101/gr.1239303
  30. Sorlie T, 2001, P NATL ACAD SCI USA, V98, P10869, DOI 10.1073/pnas.191367098
  31. Stine ZE, 2015, CANCER DISCOV, V5, P1024, DOI 10.1158/2159-8290.CD-15-0507
  32. Subramanian A, 2005, P NATL ACAD SCI USA, V102, P15545, DOI 10.1073/pnas.0506580102
  33. Terunuma A, 2014, J CLIN INVEST, V124, P398, DOI 10.1172/JCI71180
  34. Vander Heiden MG, 2017, CELL, V168, DOI 10.1016/j.cell.2016.12.039
  35. Vaquerizas JM, 2009, NAT REV GENET, V10, P252, DOI 10.1038/nrg2538
  36. Ward PS, 2012, CANCER CELL, V21, P297, DOI 10.1016/j.ccr.2012.02.014
  37. Ward PS, 2010, CANCER CELL, V17, P225, DOI 10.1016/j.ccr.2010.01.020
  38. Weinstein JN, 2013, NAT GENET, V45, P1113, DOI 10.1038/ng.2764
  39. Zack TI, 2013, NAT GENET, V45, P1134, DOI 10.1038/ng.2760

Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - ODS/03