Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy.
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 TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( Clinicaltrial.gov 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.
Radiation Oncology, Department of Oncology, University of Pisa, Pisa, Italy.
Francesco
F
Pasqualetti
Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55, 56126, Pisa, Italy.
Paola
P
Orlandi
Laboratory of Preclinical and Translational Research IRCCS-CROB Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy.
Vittorio
V
Simeon
Radiation Oncology, Department of Oncology, University of Pisa, Pisa, Italy.
Martina
M
Cantarella
Section of Pharmacology and Molecular Medicine, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Daniela
D
Giuliani
Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55, 56126, Pisa, Italy.
Teresa
T
Di Desidero
Radiation Oncology, Department of Oncology, University of Pisa, Pisa, Italy.
Alessandra
A
Gonnelli
Radiation Oncology, Department of Oncology, University of Pisa, Pisa, Italy.
Durim
D
Delishaj
Department of Clinical and Experimental Oncology, Medical Oncology I Unit, Veneto Institute of Oncology-IRCCS, Padova, Italy.
Giuseppe
G
Lombardi
Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U 1127, CNRS, UMR 7225, GH Pitié-Salpêtrièr, GH Pitié-Salpêtrièr, Sorbonne Universités, 75013, Paris, France.
Andrea
A
Sechi
Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U 1127, CNRS, UMR 7225, GH Pitié-Salpêtrièr, GH Pitié-Salpêtrièr, Sorbonne Universités, 75013, Paris, France.
Marc
M
Sanson
Department of Clinical and Experimental Oncology, Medical Oncology I Unit, Veneto Institute of Oncology-IRCCS, Padova, Italy.
Vittorina
V
Zagonel
Radiation Oncology, Department of Oncology, University of Pisa, Pisa, Italy.
Fabiola
F
Paiar
Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55, 56126, Pisa, Italy.
Romano
R
Danesi
Section of Pharmacology and Molecular Medicine, Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Salvatore
S
Guarini
Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55, 56126, Pisa, Italy. guido.bocci@med.unipi.it.
Guido
G
Bocci
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D044105:Receptor, Melanocortin, Type 4
Glioblastoma; Melanocortin receptor-4; Polymorphism; Radiotherapy; Temozolomide