Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
PLoS One. 2014 Jun 19;9(6):e100326. doi: 10.1371/journal.pone.0100326. eCollection 2014.
To investigate the association between genetic polymorphisms of growth factor-related genes and prognosis in patients with advanced esophageal squamous cell carcinoma (ESCC).
A total of 334 ESCC patients with advanced tumor stages (stages IIB, III and IV) were enrolled in the study. The genotypes of 14 candidate single nucleotide polymorphisms (SNPs) involved in growth factor-related functions were analyzed using iPLEX Gold technology from the genomic DNA of peripheral leukocytes, and were correlated with the clinical outcome of patients. Serum levels of growth factors were examined by enzyme-linked immunosorbent assay (ELISA).
The genetic polymorphisms of EGF:rs4444903, EGF:rs2237051 and VEGF:rs2010963 showed significant associations with overall survival (OS) of advanced ESCC patients (A/A+ A/G vs. GG, [HR = 0.77, 95% CI = 0.60-0.99, P = 0.039 for rs4444903; A/G+ G/G vs. A/A, [HR = 0.74, 95% CI = 0.58-0.95, P = 0.019 for rs2237051; G/G+G/C vs. C/C, [HR] inves = 0.69, 95% CI = 0.50-0.95, P = 0.023 for rs2010963). EGFR:rs2227983 and 3 SNPs of PIK3CA also showed borderline significant correlation with OS of advanced ESCC patients (P = 0.058 for rs2227983; P = 0.069, 0.091 and 0.067 for rs6443624, rs7651265 and rs7621329 of PIK3CA respectively). According to cumulative effect analysis of multiple SNPs, patients carrying 4 unfavorable genotypes exhibited more than a 3-fold increased risk of mortality. Finally, both EGF and VEGF expression levels significantly associated with patient mortality.
The genetic variants and expression levels of EGF and VEGF can serve as prognostic predictors in patients with advanced ESCC, and thus provide more information for optimizing personalized therapies for patients with ESCC.
探讨生长因子相关基因的遗传多态性与晚期食管鳞状细胞癌（ESCC）患者预后的关系。
本研究共纳入 334 例晚期肿瘤（IIB、III 和 IV 期）ESCC 患者。采用 iPLEX Gold 技术从外周血白细胞基因组 DNA 中分析 14 个候选单核苷酸多态性（SNP）的基因型，与患者的临床结局相关。采用酶联免疫吸附试验（ELISA）检测生长因子的血清水平。
EGF：rs4444903、EGF：rs2237051 和 VEGF：rs2010963 的遗传多态性与晚期 ESCC 患者的总生存期（OS）显著相关（AA/A+AG 与 GG，[HR=0.77，95%CI=0.60-0.99，P=0.039 对于 rs4444903；AG+GG 与 AA，[HR=0.74，95%CI=0.58-0.95，P=0.019 对于 rs2237051；GG+GC 与 CC，[HR=0.69，95%CI=0.50-0.95，P=0.023 对于 rs2010963）。EGFR：rs2227983 和 PIK3CA 的 3 个 SNP 也与晚期 ESCC 患者的 OS 呈临界显著相关（rs2227983，P=0.058；rs6443624、rs7651265 和 rs7621329 的 P=0.069、0.091 和 0.067）。根据多个 SNP 的累积效应分析，携带 4 个不利基因型的患者死亡风险增加了 3 倍以上。最后，EGF 和 VEGF 的表达水平与患者的死亡率显著相关。
EGF 和 VEGF 的遗传变异和表达水平可作为晚期 ESCC 患者的预后预测指标，为 ESCC 患者的个体化治疗提供更多信息。
