Genetic interaction of P2X7 receptor and VEGFR-2 polymorphisms identifies a favorable prognostic profile in prostate cancer patients.
VEGFR-2 and P2X7 receptor (P2X7R) have been described to stimulate the angiogenesis and inflammatory processes of prostate cancer. The present study has been performed to investigate the genetic interactions among VEGFR-2 and P2X7R SNPs and their correlation with overall survival (OS) in a population of metastatic prostate cancer patients. Analyses were performed on germline DNA obtained from blood samples and SNPs were investigated by real-time PCR technique. The survival dimensionality reduction (SDR) methodology was applied to investigate the genetic interaction between SNPs. One hundred patients were enrolled. The SDR software provided two genetic interaction profiles consisting of the combination between specific VEGFR-2 (rs2071559, rs11133360) and P2X7R (rs3751143, rs208294) genotypes. The median OS was 126 months (95% CI, 115.94-152.96) and 65.65 months (95% CI, 52.95-76.53) for the favorable and the unfavorable genetic profile, respectively (p < 0.0001). The genetic statistical interaction between VEGFR-2 (rs2071559, rs11133360) and P2X7R (rs3751143, rs208294) genotypes may identify a population of prostate cancer patients with a better prognosis.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Anna
A
Solini
Laboratory of Pre-Clinical and Translational Research, IRCCS - CROB Referral Cancer Center of Basilicata, Rionero in Vulture, Potenza, Italy.
Vittorio
V
Simeon
Oncology Unit 2, University Hospital of Pisa, Pisa, Italy.
Lisa
L
Derosa
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Paola
P
Orlandi
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Chiara
C
Rossi
Oncology Unit 2, University Hospital of Pisa, Pisa, Italy.
Andrea
A
Fontana
Oncology Unit 2, University Hospital of Pisa, Pisa, Italy.
Luca
L
Galli
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Teresa
T
Di Desidero
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Anna
A
Fioravanti
Division of Medical Oncology, Pontedera Hospital, Azienda USL of Pisa, Pontedera, Italy.
Sara
S
Lucchesi
Division of Medical Oncology, Pontedera Hospital, Azienda USL of Pisa, Pontedera, Italy.
Luigi
L
Coltelli
Division of Medical Oncology, Pontedera Hospital, Azienda USL of Pisa, Pontedera, Italy.
Laura
L
Ginocchi
Division of Medical Oncology, Pontedera Hospital, Azienda USL of Pisa, Pontedera, Italy.
Giacomo
G
Allegrini
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Romano
R
Danesi
Oncology Unit 2, University Hospital of Pisa, Pisa, Italy.
Alfredo
A
Falcone
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Guido
G
Bocci
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D060888:Real-Time Polymerase Chain Reaction; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D014408:Biomarkers, Tumor; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
P2X7 receptor; VEGFR-2; polymorphisms; prostate cancer; survival dimensionality reduction analysis