Evaluation of Angiogenesis-Related Genes as Prognostic Biomarkers of Bevacizumab Treated Ovarian Cancer Patients: Results from the Phase IV MITO16A/ManGO OV-2 Translational Study.
Bevacizumab treatment
angiogenesis
microRNAs
ovarian cancer
vessel density
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
14 Oct 2021
14 Oct 2021
Historique:
received:
17
09
2021
revised:
11
10
2021
accepted:
12
10
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
24
10
2021
Statut:
epublish
Résumé
Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment. Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes. High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients' survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance. The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.
Sections du résumé
BACKGROUND
BACKGROUND
Epithelial ovarian cancer (EOC) is a rare, highly lethal disease. In a subset of high grade EOC patients, maintenance therapy with the antiangiogenic drug Bevacizumab (BEV) is a valuable option. To date, no validated predictive or prognostic biomarkers exist for selecting EOC patients that might benefit from BEV treatment.
METHODS
METHODS
Immunohistochemistry and RT-qPCR evaluated the expression of seven angiogenesis-related proteins and of a twelve microRNAs angio-signature in EOC patients, treated in first line with chemotherapy plus BEV (MITO16A/ManGO OV-2 phase IV trial). Centralized statistical analyses assessed the associations between each biomarker, clinical prognostic factors and survival outcomes.
RESULTS
RESULTS
High miR-484 expression was associated with longer progression-free and overall survival. Notably, the combined expression of miR-484 and its target VEGFB identified a subset of patients that might mostly benefit from BEV treatment. No other significant correlations were found between the other analyzed biomarkers and patients' survival. The application of a shrinkage procedure to adjust for over-fitting hazard ratio estimates reduced the association significance.
CONCLUSIONS
CONCLUSIONS
The analysis of angiogenesis related biomarkers in EOC patients homogenously treated with BEV in first line provides novel insight in their prognostic value and suggests that some of them might merit to be tested as predictive markers of drug activity in dedicated randomized trials.
Identifiants
pubmed: 34680301
pii: cancers13205152
doi: 10.3390/cancers13205152
pmc: PMC8533892
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Ministero della Salute
ID : CRO Ricerca Corrente grant (linea 1)
Organisme : Ministero della Salute
ID : RF-2016-02361040
Organisme : Ministero della Salute
ID : RCR-2019-23669115
Organisme : Ministero degli Affari Esteri
ID : PGR01230
Organisme : Italian Association for Cancer Research
ID : To S.P.
Organisme : Associazione Italiana Di Oncologia Medica
ID : To S.P.
Organisme : Ministero della Salute
ID : IRCCS-G. Pascale Ricerca Corrente grant M2/7
Organisme : Italian Association for Cancer Research
ID : 20902
Organisme : University of Campania "Luigi Vanvitelli"
ID : Programma VALERE
Références
Lab Invest. 1997 Dec;77(6):607-14
pubmed: 9426398
J Clin Oncol. 2014 May 1;32(13):1302-8
pubmed: 24637997
Lancet. 2014 Oct 11;384(9951):1376-88
pubmed: 24767708
J Natl Cancer Inst. 2017 Nov 1;109(11):
pubmed: 29059427
Cells. 2020 Apr 07;9(4):
pubmed: 32272732
Development. 2018 Jul 20;145(14):
pubmed: 30030240
Cancer Lett. 2002 Feb 25;176(2):215-23
pubmed: 11804750
Lancet Oncol. 2017 Sep;18(9):1274-1284
pubmed: 28754483
Lancet Oncol. 2015 Jan;16(1):87-97
pubmed: 25481791
Lancet Oncol. 2021 Feb;22(2):267-276
pubmed: 33539744
N Engl J Med. 2016 Dec;375(22):2154-2164
pubmed: 27717299
Stat Med. 2004 Jun 15;23(11):1701-13
pubmed: 15160403
Lancet. 2019 Mar 23;393(10177):1240-1253
pubmed: 30910306
N Engl J Med. 2019 Dec 19;381(25):2416-2428
pubmed: 31851799
Dev Cell. 2011 Aug 16;21(2):193-215
pubmed: 21839917
N Engl J Med. 2011 Dec 29;365(26):2473-83
pubmed: 22204724
N Engl J Med. 2011 Dec 29;365(26):2484-96
pubmed: 22204725
Med Res Rev. 2021 Jan;41(1):586-615
pubmed: 33058230
Clin Colorectal Cancer. 2019 Dec;18(4):e370-e384
pubmed: 31402291
Curr Opin Genet Dev. 2005 Feb;15(1):102-11
pubmed: 15661540
Methods Mol Biol. 2015;1332:3-23
pubmed: 26285742
N Engl J Med. 2018 Dec 27;379(26):2495-2505
pubmed: 30345884
Curr Pharm Des. 2012;18(25):3784-92
pubmed: 22591424
Curr Mol Med. 2018;18(6):343-351
pubmed: 30411685
J Natl Cancer Inst. 2017 Nov 1;109(11):
pubmed: 29059426
Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9845-50
pubmed: 23697367
J Clin Oncol. 2019 Sep 10;37(26):2317-2328
pubmed: 31216226
N Engl J Med. 2019 Dec 19;381(25):2391-2402
pubmed: 31562799
Int J Gynecol Cancer. 2021 Jun;31(6):875-882
pubmed: 33931498