Int J Cancer 2012 Feb;130 (3): 671-6. [IF:4.926]
Host immune gene polymorphisms were associated with the prognosis of non-small-cell lung cancer in Chinese.
Dai J , Hu Z , Dong J , Xu L , Pan S , Jiang Y , Jin G , Chen Y , Shen H .
Department of Epidemiology and Biostatistics and Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
南京医科大学公共卫生学院，现代毒理学教育部重点实验室
Abstract
Laboratory-based studies showed that host immune genes could influence the prognosis of non-small-cell lung cancer (NSCLC). Therefore, genetic polymorphisms in host immune genes may serve as predictors for NSCLC clinical outcome. To test the hypothesis that functional single nucleotide polymorphisms (SNPs) in host immune genes are associated with the prognosis of NSCLC, we systematically performed a genotyping analysis for a total of 178 SNPs from 52 immune genes in a prospective case cohort of 568 NSCLC patients. Among the 178 SNPs, 24 were significantly associated with NSCLC prognosis in different genetic models and four of them were remained in the final predictive model after multivariate stepwise Cox regression, including IL-5R rs11713419 (5'-untranslated region, 5'-UTR) (P = 0.001), IL23R rs6682925 (5'-flanking region, 5'-FR) (P = 0.017), TLR1 rs5743551 (5'-FR) (P = 0.02) and TLR3 rs3775291 (Leu412Phe) (P = 0.01). We then put the above four SNPs together, and found that the risk of death was significantly increased by 124% (HR = 2.24, 95% CI: 1.33-3.75) for the patients carrying "1" unfavorable locus and by 175% (HR = 2.75, 95% CI: 1.67-4.51) for those carrying "2-4" unfavorable loci. The risk score model and time-dependent ROC analyses further support the four SNPs and clinical risk score model. The area under curve (AUC) at year 5 increased from 0.484 to 0.831 after combining the four SNPs risk score with clinical risk score. These findings indicate that potentially functional polymorphisms in immune genes may serve as prognostic markers of clinical outcome of NSCLC.
摘要：
实验研究表明宿主免疫基因会影响非小细胞肺癌(NSCLC) 的预后。因此,宿主免疫基因遗传多态性可作为预测非小细胞肺癌患者的临床结局。为了验证这一假设，宿主免疫基因的单核苷酸多态性与非小细胞肺癌患者的预后相关,我们对预期的非小细胞肺癌患者群568名患者的52种免疫基因总共178个单核苷酸多态性进行系统的分析，在178个单核苷酸变异中，不同的基因型中有24种与非小细胞肺癌患者的预后显著相关，进行多元逐步Cox回归分析后，其中仍有4种处于最终的预测模式，包括IL-5R rs11713419（5'端非编码区，5'-UTR）(P = 0.001), IL23R rs6682925 (5'调控区, 5'-FR) (P = 0.017), TLR1 rs5743551 (5'-FR) (P = 0.02) 和TLR3 rs3775291 (Leu412Phe) (P = 0.01)。然后我们将上述四个基因变异放在一起，发现携带一个不利位点的患者死亡风险显著增加了124%(HR = 2.24,95%可信区间:1.33——3.75)，携带2-4个不良位点的患者死亡风险增加了175% (HR = 2.75, 95% CI: 1.67-4.51)。风险评分模型和时间依赖性ROC分析进一步验证了四个基因变异和临床风险评分模型。将4种基因变异组合后临床风险评分第五年的曲线下面积(AUC)从0.484增加到0.831。这些研究结果表明免疫基因功能多态性可能作为非小细胞肺癌临床疗效预后标记物。
