PMID- 30856283
OWN - NLM
STAT- Publisher
LR  - 20190326
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
DP  - 2019 Mar 11
TI  - AMPK variant, a candidate of novel predictor for chemotherapy in metastatic
      colorectal cancer: A meta-analysis using TRIBE, MAVERICC and FIRE3.
LID - 10.1002/ijc.32261 [doi]
AB  - AMP-activated protein kinase (AMPK) is a key sensor of energy homeostasis and
      regulates cell metabolism, proliferation and chemotherapy/radiotherapy
      sensitivities. This study aimed to explore the relationship between the AMPK
      pathway-related single nucleotide polymorphisms (SNPs) and clinical outcomes in
      patients with metastatic colorectal cancer (mCRC). We analyzed a total of 884
      patients with mCRC enrolled in three randomized clinical trials (TRIBE, MAVERICC 
      and FIRE-3: where patients were treated with FOLFIRI, mFOLFOX6 or FOLFOXIRI
      combined with bevacizumab or cetuximab as the first-line chemotherapy). The
      association between AMPK pathway-related SNPs and clinical outcomes was analyzed 
      across the six treatment cohorts, using a meta-analysis approach. Our
      meta-analysis showed that AMPK pathway had significant associations with
      progression-free survival (PFS; p < 0.001) and overall survival (OS; p < 0.001), 
      but not with tumor response (TR; p = 0.220): PRKAA1 rs13361707 was significantly 
      associated with favorable PFS (log HR = -0.219, SE = 0.073, p = 0.003), as well
      as PRKAA1 rs10074991 (log HR = -0.215, SE = 0.073, p = 0.003), and there were
      suggestive associations of PRKAG1 rs1138908 with unfavorable OS (log HR = 0.170, 
      SE = 0.083, p = 0.041), and of UBE2O rs3803739 with unfavorable PFS (log HR =
      0.137, SE = 0.068, p = 0.042) and OS (log HR = 0.210, SE = 0.077, p = 0.006),
      although these results were not significant after false discovery rate
      adjustment. AMPK pathway-related SNPs may be predictors for chemotherapy in mCRC.
      Upon validation, our findings would provide novel insight for selecting treatment
      strategies.
CI  - (c) 2019 UICC.
FAU - Tokunaga, Ryuma
AU  - Tokunaga R
AUID- ORCID: https://orcid.org/0000-0003-4326-0315
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Cao, Shu
AU  - Cao S
AD  - Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck
      School of Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Naseem, Madiha
AU  - Naseem M
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Battaglin, Francesca
AU  - Battaglin F
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
AD  - Clinical and Experimental Oncology Department, Medical Oncology Unit 1 Veneto
      Institute of Oncology IOV-IRCCS, Padua, Italy.
FAU - Lo, Jae Ho
AU  - Lo JH
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Arai, Hiroyuki
AU  - Arai H
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Loupakis, Fotios
AU  - Loupakis F
AUID- ORCID: https://orcid.org/0000-0001-9651-0395
AD  - Clinical and Experimental Oncology Department, Medical Oncology Unit 1 Veneto
      Institute of Oncology IOV-IRCCS, Padua, Italy.
FAU - Stintzing, Sebastian
AU  - Stintzing S
AUID- ORCID: https://orcid.org/0000-0002-3297-5801
AD  - Medical Department, Divison of Oncology and Hematology (CCM), Charite
      Universitatsmedizin, Berlin, Germany.
FAU - Puccini, Alberto
AU  - Puccini A
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Berger, Martin D
AU  - Berger MD
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Soni, Shivani
AU  - Soni S
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Zhang, Wu
AU  - Zhang W
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Mancao, Christoph
AU  - Mancao C
AD  - Oncology Biomarker Development, Genentech Inc., Basel, Switzerland.
FAU - Salhia, Bodour
AU  - Salhia B
AD  - Department of Translational Genomics, Norris Comprehensive Cancer Center, Keck
      School of Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Mumenthaler, Shannon M
AU  - Mumenthaler SM
AD  - Lawrence J. Ellison Institute for Transformative Medicine, Norris Comprehensive
      Cancer Center, Keck School of Medicine, University of Southern California, Los
      Angeles, CA, USA.
FAU - Weisenberger, Daniel J
AU  - Weisenberger DJ
AD  - Department of Biochemistry and Molecular Medicine, Norris Comprehensive Cancer
      Center, Keck School of Medicine, University of Southern California, Los Angeles, 
      CA, USA.
FAU - Liang, Gangning
AU  - Liang G
AD  - Department of Urology, Norris Comprehensive Cancer Center, Keck School of
      Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Cremolini, Chiara
AU  - Cremolini C
AD  - Department of Medical Oncology, University of Pisa, Pisa, Italy.
FAU - Heinemann, Volker
AU  - Heinemann V
AD  - Medical Department, Divison of Oncology and Hematology (CCM), Charite
      Universitatsmedizin, Berlin, Germany.
FAU - Falcone, Alfredo
AU  - Falcone A
AD  - Department of Medical Oncology, University of Pisa, Pisa, Italy.
FAU - Millstein, Joshua
AU  - Millstein J
AD  - Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck
      School of Medicine, University of Southern California, Los Angeles, CA, USA.
FAU - Lenz, Heinz-Josef
AU  - Lenz HJ
AUID- ORCID: https://orcid.org/0000-0001-8316-4411
AD  - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of 
      Medicine, University of Southern California, Los Angeles, CA, USA.
LA  - eng
GR  - Dhont Family Foundation
GR  - P30CA014089/National Cancer Institute
GR  - Uehara Memorial Foundation
GR  - Daniel Butler Research Fund
GR  - San Pedro Peninsula Cancer Guild
PT  - Journal Article
DEP - 20190311
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
OTO - NOTNLM
OT  - AMPK
OT  - SNP
OT  - chemotherapy
OT  - metastatic colorectal cancer
OT  - variant
EDAT- 2019/03/12 06:00
MHDA- 2019/03/12 06:00
CRDT- 2019/03/12 06:00
PHST- 2018/10/11 00:00 [received]
PHST- 2019/01/23 00:00 [revised]
PHST- 2019/02/13 00:00 [accepted]
PHST- 2019/03/12 06:00 [pubmed]
PHST- 2019/03/12 06:00 [medline]
PHST- 2019/03/12 06:00 [entrez]
AID - 10.1002/ijc.32261 [doi]
PST - aheadofprint
SO  - Int J Cancer. 2019 Mar 11. doi: 10.1002/ijc.32261.