PMID- 30194194 OWN - NLM STAT- MEDLINE DCOM- 20180917 LR - 20180917 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 38 IP - 9 DP - 2018 Sep TI - Predicting Response to Standard First-line Treatment in High-grade Serous Ovarian Carcinoma by Angiogenesis-related Genes. PG - 5393-5400 LID - 10.21873/anticanres.12869 [doi] AB - BACKGROUND/AIM: Predicting response to treatment in high-grade serous ovarian carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for first-line chemotherapy, based on a combination of carboplatin and paclitaxel, achieves a high response rate. However, the development of drug resistance is one of the major limitations to efficacy. Therefore, identification of biomarkers able to predict response to chemotherapy in patients with HGSOC is a critical step for prognosis and treatment of the disease. Several studies suggest that angiogenesis is an important process in the development of ovarian carcinoma and chemoresistance. The aim of this study was to identify a profile of angiogenesis-related genes as a biomarker for response to first-line chemotherapy in HGSOC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples from 39 patients with HGSOC who underwent surgical cytoreduction and received a first-line chemotherapy with carboplatin and paclitaxel were included in this study. Expression levels of 82 angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. RESULTS: Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated with response to treatment. Multivariable analysis by Lasso-penalized Cox regression generated a model with the combined expression of seven genes [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8 (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics curve (0.679) and cross-validated Kaplan-Meier survival curves were used to estimate the accuracy of these predictors. CONCLUSION: An angiogenesis-related gene expression profile useful for response prediction in HGSOC was identified, supporting the important role of angiogenesis in HGSOC. CI - Copyright(c) 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Mendiola, Marta AU - Mendiola M AD - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Center for Biomedical Research in the Cancer Network (Centro de Investigacion Biomedica en Red de Cancer, CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. FAU - Redondo, Andres AU - Redondo A AD - Department of Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Translational Oncology Research Laboratory, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Faculty of Medicine, Autonomous University of Madrid (UAM), Madrid, Spain. FAU - Heredia-Soto, Victoria AU - Heredia-Soto V AD - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Center for Biomedical Research in the Cancer Network (Centro de Investigacion Biomedica en Red de Cancer, CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. FAU - Herranz, Jesus AU - Herranz J AD - Bioinformatics Unit, IMDEA Food Institute, Madrid, Spain. FAU - Berjon, Alberto AU - Berjon A AD - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Department of Pathology, La Paz University Hospital (IdiPAZ), Madrid, Spain. FAU - Hernandez, Alicia AU - Hernandez A AD - Faculty of Medicine, Autonomous University of Madrid (UAM), Madrid, Spain. AD - Department of Gynecology and Obstetrics, La Paz University Hospital (IdiPAZ), Madrid, Spain. FAU - Miguel-Martin, Maria AU - Miguel-Martin M AD - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain. FAU - Crespo, Roberto AU - Crespo R AD - Translational Oncology Research Laboratory, La Paz University Hospital (IdiPAZ), Madrid, Spain. FAU - Barriuso, Jorge AU - Barriuso J AD - Division of Molecular and Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, University of Manchester, Manchester, U.K. FAU - Cruz, Patricia AU - Cruz P AD - Department of Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid, Spain. FAU - Yebenes, Laura AU - Yebenes L AD - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Department of Pathology, La Paz University Hospital (IdiPAZ), Madrid, Spain. FAU - Pelaez-Garcia, Alberto AU - Pelaez-Garcia A AD - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain. FAU - Castelo, Beatriz AU - Castelo B AD - Department of Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Translational Oncology Research Laboratory, La Paz University Hospital (IdiPAZ), Madrid, Spain. FAU - DE Molina, Ana Ramirez AU - DE Molina AR AD - Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, Madrid, Spain. FAU - Feliu, Jaime AU - Feliu J AD - Center for Biomedical Research in the Cancer Network (Centro de Investigacion Biomedica en Red de Cancer, CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. AD - Department of Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Translational Oncology Research Laboratory, La Paz University Hospital (IdiPAZ), Madrid, Spain. AD - Faculty of Medicine, Autonomous University of Madrid (UAM), Madrid, Spain. AD - UAM-AMGEN Chair, Autonomous University of Madrid (UAM), Madrid, Spain. FAU - Hardisson, David AU - Hardisson D AD - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain david.hardisson@salud.madrid.org. AD - Faculty of Medicine, Autonomous University of Madrid (UAM), Madrid, Spain. AD - Department of Pathology, La Paz University Hospital (IdiPAZ), Madrid, Spain. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Angiogenic Proteins) RN - 0 (Biomarkers, Tumor) RN - BG3F62OND5 (Carboplatin) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Angiogenic Proteins/*genetics MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Area Under Curve MH - Biomarkers, Tumor/*genetics MH - Carboplatin/administration & dosage MH - Clinical Decision-Making MH - Cytoreduction Surgical Procedures MH - Female MH - Gene Expression Profiling/*methods MH - Humans MH - Kaplan-Meier Estimate MH - Middle Aged MH - Multivariate Analysis MH - Neoplasm Grading MH - Neoplasms, Cystic, Mucinous, and Serous/*drug therapy/*genetics/pathology MH - Neovascularization, Pathologic/*genetics MH - Ovarian Neoplasms/*drug therapy/*genetics/pathology MH - Paclitaxel/administration & dosage MH - Patient Selection MH - Precision Medicine/*methods MH - Predictive Value of Tests MH - Proportional Hazards Models MH - ROC Curve MH - Risk Factors MH - Transcriptome OTO - NOTNLM OT - Ovarian cancer OT - angiogenesis OT - chemotherapy OT - gene-expression profile OT - high-grade serous carcinoma OT - response prediction EDAT- 2018/09/09 06:00 MHDA- 2018/09/18 06:00 CRDT- 2018/09/09 06:00 PHST- 2018/07/12 00:00 [received] PHST- 2018/07/25 00:00 [revised] PHST- 2018/07/27 00:00 [accepted] PHST- 2018/09/09 06:00 [entrez] PHST- 2018/09/09 06:00 [pubmed] PHST- 2018/09/18 06:00 [medline] AID - 38/9/5393 [pii] AID - 10.21873/anticanres.12869 [doi] PST - ppublish SO - Anticancer Res. 2018 Sep;38(9):5393-5400. doi: 10.21873/anticanres.12869.