PMID- 30807642
OWN - NLM
STAT- Publisher
LR  - 20190323
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
DP  - 2019 Feb 26
TI  - CA125 over-release behavior following a 75-g oral glucose test as a predictive
      biomarker of multidrug resistance in patients with ovarian cancer.
LID - 10.1002/ijc.32237 [doi]
AB  - Multidrug resistance is a major cause of death in patients with ovarian cancer.
      To improve patient survival, we developed a novel, noninvasive and convenient
      tool, the 75-gram oral glucose (75gOG)-stimulated CA125 test, to monitor cancer
      chemoresistance in real time. Our in vitro proof-of-principal experiments
      revealed that post-75gOG glucose and insulin peaks can synergistically increase
      cancer-derived CA125 levels, and the increase in CA125 secretion (DeltaCA125) is 
      correlated with the overactivation of the insulin receptor (IR)-PI3K-Akt axis and
      increases (DeltaIC50 s) in cisplatin/taxol IC50 s. Correspondingly, among the 93 
      patients enrolled, post-75gOG CA125 over-release (i.e., enhanced DeltaCA125)
      behavior was associated with overexpression of the IR-PI3K-Akt pathway and its
      downstream components, namely, IR, pAkt, pS6 and GLUT4, in cancer specimens.
      Furthermore, both pre- and postsurgical 75gOG CA125 tests demonstrated that CA125
      over-release showed excellent prediction efficacy on the chemoresistance
      potential of ovarian cancer; notably, the former indicated the need for an
      optimal debulking surgery, and the latter suggested the use of IR-PI3K-Akt
      inhibitors. Both test results possess independent prognostic significance for the
      2-year progression-free survival (PFS) and overall survival (OS) of patients. The
      odds ratios and corresponding 95% confidence intervals (95% CIs) were 2.680 (95% 
      CI: 1.393-5.156) for patients with CA125 over-release behavior evidenced by a
      presurgical 75gOG CA125 test or 3.822 (95% CI: 1.942-7.522) for that evidenced by
      a postsurgical test in PFS; and 3.320 (95% CI: 1.508-7.309) for patients with
      CA125 over-release behavior evidenced by a presurgical test or 5.212 (95% CI:
      2.241-12.121) for that evidenced by a postsurgical test in OS.
CI  - (c) 2019 UICC.
FAU - He, Yifeng
AU  - He Y
AUID- ORCID: https://orcid.org/0000-0003-0764-8806
AD  - Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine,
      Shanghai Jiao Tong University, Shanghai, China.
AD  - Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of
      Medicine, Shanghai Jiao Tong University, Shanghai, China.
AD  - Tumor Microenvironment and Metastasis Program, The Wistar Institute, University
      of Pennsylvania, Philadelphia, PA.
FAU - Gu, Zhuowei
AU  - Gu Z
AD  - Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine,
      Shanghai Jiao Tong University, Shanghai, China.
AD  - Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of
      Medicine, Shanghai Jiao Tong University, Shanghai, China.
FAU - Zhu, Qiujing
AU  - Zhu Q
AD  - Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine,
      Shanghai Jiao Tong University, Shanghai, China.
AD  - Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of
      Medicine, Shanghai Jiao Tong University, Shanghai, China.
FAU - Chen, Mo
AU  - Chen M
AD  - Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University,
      Shanghai, China.
FAU - He, Chenghui
AU  - He C
AD  - Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine,
      Shanghai Jiao Tong University, Shanghai, China.
AD  - Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of
      Medicine, Shanghai Jiao Tong University, Shanghai, China.
FAU - Huang, Yuting
AU  - Huang Y
AD  - Children's Research Institute, Children's National Medical Center, Washington,
      WA.
FAU - Li, Qing
AU  - Li Q
AD  - Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine,
      Shanghai Jiao Tong University, Shanghai, China.
AD  - Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of
      Medicine, Shanghai Jiao Tong University, Shanghai, China.
AD  - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute,
      Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai,
      China.
FAU - Di, Wen
AU  - Di W
AD  - Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine,
      Shanghai Jiao Tong University, Shanghai, China.
AD  - Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of
      Medicine, Shanghai Jiao Tong University, Shanghai, China.
AD  - State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute,
      Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai,
      China.
LA  - eng
GR  - 2016YFC1303100/National Key Research and Development Program of China
GR  - 81472426/National Natural Science Foundation of China
GR  - 81572548/National Natural Science Foundation of China
GR  - 81772770/National Natural Science Foundation of China
GR  - 15441905700/Science and Technology Commission of Shanghai Municipality
GR  - 15DZ1940502/Science and Technology Commission of Shanghai Municipality
GR  - 15GWZK0701/Shanghai Municipal Commission of Health and Family Planning
GR  - 2017ZZ02016/Shanghai Municipal Commission of Health and Family Planning
GR  - ZY(2018-2020)-FWTX-3006/Shanghai Municipal Commission of Health and Family
      Planning
PT  - Journal Article
DEP - 20190226
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
OTO - NOTNLM
OT  - 2-year survival
OT  - Akt
OT  - CA125
OT  - GLUT4
OT  - IR
OT  - OGTT
OT  - PI3K
OT  - chemoresistance
OT  - insulin
OT  - ovarian cancer
EDAT- 2019/02/27 06:00
MHDA- 2019/02/27 06:00
CRDT- 2019/02/27 06:00
PHST- 2018/06/13 00:00 [received]
PHST- 2019/02/11 00:00 [accepted]
PHST- 2019/02/27 06:00 [pubmed]
PHST- 2019/02/27 06:00 [medline]
PHST- 2019/02/27 06:00 [entrez]
AID - 10.1002/ijc.32237 [doi]
PST - aheadofprint
SO  - Int J Cancer. 2019 Feb 26. doi: 10.1002/ijc.32237.