A Prognostic and Carboplatin Response Predictive Model in Ovarian Cancer: A Mono-Institutional Retrospective Study Based on Clinics and Pharmacogenomics
Nicoletta Staropoli,
Mariamena Arbitrio,
Angela Salvino,
Francesca Scionti,
Domenico Ciliberto,
Rossana Ingargiola,
Caterina Labanca,
Giuseppe Agapito,
Eleonora Iuliano,
Vito Barbieri,
Maria Cucè,
Valeria Zuccalà,
Mario Cannataro,
Pierfrancesco Tassone,
Pierosandro Tagliaferri
Affiliations
Nicoletta Staropoli
Medical Oncology Unit, AOU Mater Domini, 88100 Catanzaro, Italy
Mariamena Arbitrio
Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 88100 Catanzaro, Italy
Angela Salvino
Medical Oncology Unit, AOU Mater Domini, 88100 Catanzaro, Italy
Francesca Scionti
Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98125 Messina, Italy
Domenico Ciliberto
Medical Oncology Unit, AOU Mater Domini, 88100 Catanzaro, Italy
Rossana Ingargiola
Department of Experimental and Clinical Medicine, Magna Græcia University, 88100 Catanzaro, Italy
Caterina Labanca
Department of Experimental and Clinical Medicine, Magna Græcia University, 88100 Catanzaro, Italy
Giuseppe Agapito
Department of Law, Economics and Sociology, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy
Eleonora Iuliano
Department of Experimental and Clinical Medicine, Magna Græcia University, 88100 Catanzaro, Italy
Vito Barbieri
Medical Oncology Unit, “Pugliese-Ciaccio” Hospital, 88100 Catanzaro, Italy
Maria Cucè
Medical Oncology Unit, AOU Mater Domini, 88100 Catanzaro, Italy
Valeria Zuccalà
Pathology Unit, “Pugliese-Ciaccio” Hospital, 88100 Catanzaro, Italy
Mario Cannataro
Data Analytics Research Center, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy
Pierfrancesco Tassone
Medical Oncology Unit, AOU Mater Domini, 88100 Catanzaro, Italy
Pierosandro Tagliaferri
Medical Oncology Unit, AOU Mater Domini, 88100 Catanzaro, Italy
Carboplatin is the cornerstone of ovarian cancer (OC) treatment, while platinum-response, dependent on interindividual variability, is the major prognostic factor for long-term outcomes. This retrospective study was focused on explorative search of genetic polymorphisms in the Absorption, Distribution, Metabolism, Excretion (ADME) genes for the identification of biomarkers prognostic/predictive of platinum-response in OC patients. Ninety-two advanced OC patients treated with carboplatin-based therapy were enrolled at our institution. Of these, we showed that 72% of patients were platinum-sensitive, with a significant benefit in terms of OS (p = 0.001). We identified an inflammatory-score with a longer OS in patients with lower scores as compared to patients with the maximum score (p = 0.001). Thirty-two patients were genotyped for 1931 single nucleotide polymorphisms (SNPs) and five copy number variations (CNVs) by the DMET Plus array platform. Among prognostic polymorphisms, we found a potential role of UGT2A1 both as a predictor of platinum-response (p = 0.01) and as prognostic of survival (p = 0.05). Finally, we identified 24 SNPs related to OS. UGT2A1 correlates to an “inflammatory-score” and retains a potential prognostic role in advanced OC. These data provide a proof of concept that warrants further validation in follow-up studies for the definition of novel biomarkers in this aggressive disease.