Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy

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作   者：

Pasqualetti, Francesco;  Orlandi, Paola;  Simeon, Vittorio;  Cantarella, Martina;  Giuliani, Daniela;  Di Desidero, Teresa;  Gonnelli, Alessandra;  Delishaj, Durim;  Lombardi, Giuseppe;  Sechi, Andrea;  Sanson, Marc;  Zagonel, Vittorina;  Paiar, Fabiola;  Danesi, Romano;  Guarini, Salvatore;  Bocci, Guido; 

作者机构：

Ctr Rech Inst Cerveau & Moelle Epiniere;  I-56126 Pisa;  Via Roma 55;  IRCCS CROB Ctr Riferimento Oncol Basilicata;  Dept Clin & Expt Med;  Sorbonne Univ;  Modena;  Sorbonne Univ;  Pisa;  Padua;  GH Pitie;  Lab Preclin & Translat Res;  Italy;  Sect Pharmacol & Mol Med;  Med Oncol Unit 1;  Dept Biomed Metab & Neural Sci;  Univ Pisa;  Rionero In Vulture;  Dept Oncol;  Radiat Oncol;  INSERM U1127;  Veneto Inst Oncol IRCCS;  Univ Modena & Reggio Emilia;  Dept Clin & Expt Oncol;  Div Pharmacol; 

关键词：

Glioblastoma;  Temozolomide;  Radiotherapy;  Melanocortin receptor-4;  Polymorphism; 

期刊名称：

Molecular Neurobiology

i s s n：

0893-7648

年卷期：

2018 年 55 卷 2 期

页   码：

1396-1404

页   码：

摘   要：

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqManA (R) SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( identifier NCT02458508). The median progression-free survival (PFS) and median overall survival (OS) of these patients were 9.54 (95% CI 5.4-14.3) months and 24.9 (95% CI 17.8-34.6) months, respectively. The MC4R rs489693 AA genotype was significantly associated with a shorter PFS and OS. Indeed, with regard to PFS, patients harboring the rs489693 AA genotype had a median PFS of 2.99 months whereas patients with AC/CC genotypes had a median PFS of 10.82 months (P = 0.009). Interestingly, the rs489693 AA patients also had a lower median OS as compared with the median OS of the AC/CC genotypes (10.75 vs. 29.5 months, respectively, P = 0.0001). This study suggests that the MC4R rs489693 AA genotype is significantly associated with a shorter PFS and OS in patients treated with radiotherapy and temozolomide. These findings represent a relevant effort to identify novel clinical markers for RT-CT therapy in GBM to be validated in future pharmacogenetic clinical trials.