title: The relationship of kinase insert domain receptor gene polymorphisms and clinical outcome in advanced hepatocellular carcinoma patients treated with sorafenib.
abstract: Kinase insert domain receptor (KDR) is the principal receptor that promotes the pro-angiogenic action of vascular endothelial growth factor and has been the principal target of anti-angiogenic therapies. Our aim was to determine whether single-nucleotide polymorphisms (SNPs) in KDR gene are associated with clinical outcomes after first-line sorafenib therapy in advanced hepatocellular carcinoma (HCC). The SNPs in KDR were tested in 78 advanced HCC patients receiving first-line sorafenib. Correlations with clinicopathological features and survival were analyzed. Patients with AA genotype of rs1870377 and AA genotype of rs2305948 were significantly associated with a better response and longer time to progression (TTP) (5.8 vs 4.0 months, P=0.001; 5.8 vs 4.5 months, P=0.016, respectively). Patients harboring AA genotype in rs1870377 and TT/TC genotype in rs2071559 had a longer overall survival (OS) (15.0 vs 9.6 months, P=0.001; 13.0 vs 9.0 months, P=0.007, respectively). At multivariate analysis, major vascular invasion and rs1870377 were independent factors in TTP and performance status, rs1870377, and rs2071559 were independent factors in OS. Our results suggest that SNPs in KDR gene can predict clinical outcome in advanced HCC patients receiving first-line sorafenib.
authors.affiliation: Southern Medical University, Guangzhou, China.
authors.forename: You-Bing
authors.initials: YB
authors.lastname: Zheng
authors.forename: Mei-Xiao
authors.initials: MX
authors.lastname: Zhan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Huang
authors.forename: Xu
authors.initials: X
authors.lastname: He
authors.forename: Si-Rui
authors.initials: SR
authors.lastname: Fu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Bao-Shan
authors.initials: BS
authors.lastname: Hu
authors.forename: Li-Gong
authors.initials: LG
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D000077157:Sorafenib; D015996:Survival Rate; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D040301:Vascular Endothelial Growth Factor Receptor-2