Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients

被引:38
作者
Mignogna, Chiara [1 ]
Staropoli, Nicoletta [2 ]
Botta, Cirino [3 ]
De Marco, Carmela [4 ]
Rizzuto, Antonia [5 ]
Morelli, Michele [4 ]
Di Cello, Annalisa [4 ]
Franco, Renato [6 ]
Camastra, Caterina [1 ]
Presta, Ivan [1 ]
Malara, Natalia [1 ]
Salvino, Angela [2 ]
Tassone, Pierfrancesco [3 ]
Tagliaferri, Pierosandro [2 ]
Barni, Tullio [4 ]
Donato, Giuseppe [1 ]
Di Vito, Anna [4 ]
机构
[1] Magna Graecia Univ Catanzaro, Sch Med, Pathol Unit, Dept Hlth Sci, Viale Europa, I-88100 Catanzaro, Italy
[2] Magna Graecia Univ Catanzaro, Sch Med, Dept Expt & Clin Med, Med Oncol, Viale Europa, I-88100 Catanzaro, Italy
[3] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Translat Med Oncol Unit, Catanzaro, Italy
[4] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy
[5] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Catanzaro, Italy
[6] Univ Naples 2, Dept Mental & Phys Hlth & Prevent Med, Naples, Italy
关键词
High-grade serous ovarian carcinoma (HGSOC); AURKA; Platinum; Therapy; Prognosis; PEGYLATED LIPOSOMAL DOXORUBICIN; BREAST-CANCER; FUNCTIONAL POLYMORPHISM; SUSCEPTIBILITY GENE; PANCREATIC-CANCER; PHOSPHORYLATION; AURKA; OVEREXPRESSION; IDENTIFICATION; AMPLIFICATION;
D O I
10.1186/s13048-016-0238-7
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:8
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