Marta Mendiola1,2, Andrés Redondo3,4,5, Victoria Heredia-Soto1,2, Jesús Herranz6, Alberto Berjón1,7, Alicia Hernández5,8, María Miguel-Martín1, Roberto Crespo4, Jorge Barriuso9, Patricia Cruz3, Laura Yébenes1,7, Alberto Peláez-García1, Beatriz Castelo3,4, Ana Ramírez DE Molina10, Jaime Feliu2,3,4,5,11, David Hardisson12,5,7. 1. Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain. 2. Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. 3. Department of Medical Oncology, La Paz University Hospital (IdiPAZ), Madrid, Spain. 4. Translational Oncology Research Laboratory, La Paz University Hospital (IdiPAZ), Madrid, Spain. 5. Faculty of Medicine, Autonomous University of Madrid (UAM), Madrid, Spain. 6. Bioinformatics Unit, IMDEA Food Institute, Madrid, Spain. 7. Department of Pathology, La Paz University Hospital (IdiPAZ), Madrid, Spain. 8. Department of Gynecology and Obstetrics, La Paz University Hospital (IdiPAZ), Madrid, Spain. 9. Division of Molecular and Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, University of Manchester, Manchester, U.K. 10. Molecular Oncology and Nutritional Genomics of Cancer Group, IMDEA Food Institute, Madrid, Spain. 11. UAM-AMGEN Chair, Autonomous University of Madrid (UAM), Madrid, Spain. 12. Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital (IdiPAZ), Madrid, Spain david.hardisson@salud.madrid.org.
Abstract
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. Copyright
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. Copyright
Authors: Victoria Heredia-Soto; Javier Escudero; María Miguel; Patricia Ruiz; Alejandro Gallego; Alberto Berjón; Alicia Hernández; Marta Martínez-Díez; Shuyu Zheng; Jing Tang; David Hardisson; Jaime Feliu; Andrés Redondo; Marta Mendiola Journal: Front Oncol Date: 2022-03-17 Impact factor: 6.244