title: Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.
abstract: High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment.
authors.affiliation: Department of Health Science, Pathology Unit, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy. mignogna@unicz.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mignogna
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Oncology, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy. nicolettastaropoli@gmail.com.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Staropoli
authors.affiliation: Translational Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Cirino
authors.initials: C
authors.lastname: Botta
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: De Marco
authors.affiliation: Department of Medical and Surgical Sciences, Magna Græcia University, Catanzaro, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Rizzuto
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Morelli
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Cello
authors.affiliation: Department of Mental and Physical Health and Preventive Medicine, Second University of Naples, Naples, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.affiliation: Department of Health Science, Pathology Unit, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Camastra
authors.affiliation: Department of Health Science, Pathology Unit, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Presta
authors.affiliation: Department of Health Science, Pathology Unit, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Malara
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Oncology, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Salvino
authors.affiliation: Translational Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.affiliation: Department of Experimental and Clinical Medicine, Medical Oncology, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Barni
authors.affiliation: Department of Health Science, Pathology Unit, Magna Græcia University of Catanzaro, Medical School, Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Donato
authors.affiliation: Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Vito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D064096:Aurora Kinase A / Q000235:genetics* / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D010984:Platinum / Q000494:pharmacology*; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D010984:Platinum; D064096:Aurora Kinase A
keywords: AURKA; High-grade serous ovarian carcinoma (HGSOC); Platinum; Prognosis; Therapy