NRP‑1 and KDR polymorphisms are associated with survival time in patients with advanced gastric cancer

Abstract

Neuropilin-1 (NRP-1), a member of the NRP-family, has been reported to be vital for tumor angiogenesis, growth and metastasis. As a co-receptor of vascular endothelial growth factor (VEGF), NRP-1 can bind to VEGF and meditate vascular development through the VEGF-VEGF receptor 2 (VEGFR2) signaling pathway. Furthermore, NRP-1 is capable of binding with platelet-derived growth factor (PDGF) to regulate the PDGF-PDGF receptor (PDGR) signaling pathway in tumor angiogenesis. In the present study, The DNA was obtained from the paraffin-embedded tissues of patients with advanced gastric cancer (AGC), amplified using PCR and subsequently sequenced to determine the polymorphisms within NRP-1, VEGFR2 [kinase insert domain receptor (KDR)] and PDGF. The effect of the functional polymorphism of the aforementioned genes on the overall survival (OS) and progression-free survival (PFS) of 81 patients with advanced gastric cancer was examined. Three single nucleotide polymorphisms (SNPs) of KDR were significantly associated with clinical outcomes. The rs1870377 TT genotype was positively associated with longer OS and PFS times compared with the AA+AT genotype (PFS, P=0.012; OS, P=0.038), the rs7692791 wild-type TT genotype was positively associated with longer PFS time and the rs2034965 AA+GA genotype was associated with shorter OS time (P=0.034). With regards to the SNPs of NRP-1, the rs2065364 AA genotype was significantly associated with improved OS and PFS times (PFS, P=0.023; OS, P=0.045). Following multivariate analysis using Cox proportional hazards regression models, patients with the KDR rs7692791 TT genotype experienced a longer PFS time compared with those with the CT genotype (P=0.016), and patients with the NRP-1 rs2065364 variant-type AA genotype still experienced a longer PFS time compared with those patients with the AG+GG genotypes (P=0.006). Regarding OS, the results demonstrated that the KDR rs2034965 AG+GG genotypes presented with a significant reduction in OS time (P=0.029), and that the KDR rs1870377 AT+AA genotypes had worse OS times compared with the wild-type TT genotype (P=0.021). In addition, increased mortality risk and AGC progression were significantly associated with the number of adverse alleles for combinations of NRP-1 rs2065364 and KDR rs1870377. In conclusion, the data from the present study demonstrated that the selected KDR and NRP-1 gene polymorphisms may be potential prognostic biomarkers in AGC.

Expression Profile and Diagnostic Significance of MicroRNAs in Papillary Thyroid Cancer

“…The dysregulation of miR-221, miR-222, and miR-146 has been implicated in KIT downregulation [ 77 ]. KDR is a tyrosine kinase whose overexpression in PTC was described [ 78 ]. NRAS encodes the N-ras protein responsible for regulating cell division.…”

Neuropilin-1 as a Potential Biomarker of Prognosis and Invasive-Related Parameters in Liver and Colorectal Cancer: A Systematic Review and Meta-Analysis of Human Studies

“…The use of meta-analysis has shown to be a valuable tool for assessing the reliability of overexpressed proteins as tumor biomarkers by previous studies performed on CRC and liver cancer [ 36 , 37 , 38 ]. Although a number of investigations showing this potential correlation in other tumor types have been published [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ], no previous study has evaluated the role of NRP1 as a prognostic biomarker in CRC and liver cancer patients through meta-analysis. The overexpression of NRP1 in tumor tissue has been correlated with worse prognosis in gastric cancer [ 39 , 40 ], cervical cancer [ 42 ], ovarian carcinoma [ 43 ], breast cancer [ 44 ], non-small cell lung cancer (NSCLC) [ 45 ], osteosarcoma [ 47 ], bladder cancer [ 46 ], glioma [ 49 ], nasopharyngeal carcinoma [ 48 ], and pancreatic ductal adenocarcinoma [ 41 ], among others.…”

Bioinformatics analysis to screen and identify key biomarkers of papillary renal cell carcinoma

“…[17] KDR polymorphism is associated with survival time in patients with advanced gastric cancer. [18] The CXCL12/CXCR4 axis promotes the development, invasion and metastasis of pancreatic cancer by managing the tumor microenvironment. [19] Abnormal (pro)REN receptor expression promoted the occurrence of CRC through the Wnt/ catenin signaling pathway.…”