Genetic variants in the KDR gene is associated with the prognosis of transarterial chemoembolization treated hepatocellular carcinoma
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Kinase insert domain receptor (KDR) is the principal receptor that promotes the proangiogenic action of vascular endothelial growth factor and is involved in the tumorigenesis and progression of many malignancies, including hepatocellular carcinoma (HCC). Single-nucleotide polymorphisms (SNPs) of KDR have been reported to be with the risk and prognosis of several malignancies. Our aim was to determine whether SNPs in KDR gene are associated with clinical outcomes in HCC patients treated with transcatheter arterial chemoembolization. A total of 192 HCC patients were tested for KDR SNPs, and the SNP results were correlated with progression-free survival (PFS) and overall survival (OS). The association of the SNPs with the overall survival (OS) of patients was assessed by Kaplan–Meier method, and then Cox proportional hazards model was used to assess the variables resulted significant at univariate analysis. No significant differences were found in correlation between KDR SNPs and patients’ PFS. Our data showed that genotype AA + TA of rs1870377 and genotype CC + TC of rs2071559 were significantly associated with overall survival of HCC patients (P < 0.001 and P < 0.001, respectively) and remained as significant predictors for OS adjusting for high level of serum AFP (>400 μg/L), existence of portal vein tumor thrombus, and high BCLC stage (HR = 0.61; 95 % CI, 0.36–0.88; P = 0.003 and HR = 0.54; 95 % CI, 0.40–0.94; P = 0.002, respectively). Our results suggest that SNPs rs1870377 and rs2071559 in the KDR gene may serve as independent prognosis biomarkers for unresectable HCC patient, which warranted further validating investigation.
KeywordsKDR Hepatocellular carcinoma Prognosis Single-nucleotide polymorphism
This study was supported by grants 2011A030400009 from Technology Foundation of Guangdong Province, China, and S2012010010569 from Natural Science Foundation of Guangdong Province, China.
Conflicts of interest
- 10.Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26:4672–8.PubMedCentralPubMedCrossRefGoogle Scholar
- 13.Scartozzi M, Faloppi L, Svegliati BG, Loretelli C, Piscaglia F, Iavarone M, et al. VEGF and VEGFR genotyping in the prediction of clinical outcome for HCC patients receiving sorafenib: The ALICE-1 study. Int J Cancer. 2014.Google Scholar
- 20.Matsumoto T, Claesson-Welsh L. VEGF receptor signal transduction. Sci STKE. 2001;2001:e21.Google Scholar