肝细胞癌患者外周血PD-L1基因多态性与肝细胞癌易感性及预后关系研究

摘要

Objective To investigate the polymorphism of programmed death-ligand 1(PD-L1)gene in susceptibility and prognosis of patients with hepatocellular carcinoma(HCC). Methods 100 patients with HCC and 100 healthy persons were recruited in our hospital between January 2010 and June 2015. The peripheral blood were collected to assay the single nucleotide polymorphisms(SNP),including rs4143185,rs17718883 and rs28906583,of PD-L1 gene by direct sequencing and polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP). Results The AC heterozygous mutation gene of rs2890658 reduced the risk of liver cancer susceptibility(OR=0.391,P<0.05),and the CG heterozygous mutation of rs17718883 also reduced the risk of liver cancer susceptibility(OR=0.009,P<0.05);the median survival times of 3 genotypes(AA,AC and CC)of rs2890658 were 18(15,21)m,20(16,22)m and 19(15,21)m,no significant differences among(P>0.05);the median survival time in combination of genotype AC and CC was 20(16,23)m,much longer than carrying genotype AA(P<0.05);there were significantly differences among survival times in individuals carrying CC,GC and GC of rs4143185 gene [16(13,19)m,20(15,23)m and 17(15,21)m,respectively,P<0.05],and the survival time in persons carrying combination of CG and GG was 21(17,24)m,much longer than those carrying CC(P<0.05);COX regression analysis showed that patients carrying mutant genes of rs4143185 had a good prognosis (HR<1,P<0.05). Conclusion The detection of blood PD-L1 gene polymorphism might be useful in clinical practice in screening individuals with high risk of HCC susceptibility and in forecasting the prognosis of patients with HCC.%目的 探讨肝细胞癌(HCC)患者血程序性死亡配体(PD-L)1基因多态性与易感性和预后之间的关系.方法2010年1月~2015年6月诊治的HCC患者100例和肝功能正常的正常人100例,采集外周血,采用直接测序法和聚合酶链反应- 单链构象多态性分析(PCR-SSCP)法检测PD-L1基因rs4143185、rs17718883和rs28906583三个位点的单核苷酸多态性(SNP),分析其与肝细胞癌易感性和预后之间的关系.结果 携带rs2890658的AC杂合突变基因可以降低肝细胞癌的发病风险(OR=0.391,P<0.05),携带rs17718883的CG杂合突变基因也会降低肝细胞癌的发病风险(OR=0.009,P<0.05);rs2890658位点的3个基因型AA、AC和CC的中位生存时间分别为18(15,21)m、20(16,22)m和19(15,21)m,组间差异无统计学意义(P>0.05),合并AC和CC基因型者,中位生存时间为20(16,23)m,明显比AA基因型者长,差异有统计学意义(P<0.05);携带rs4143185位点的3个基因型CC、GC和GC者中位生存时间分别为16(13,19)m、20(15,23)m和17(15,21)m,组间差异有统计学意义(P<0.05),合并CG+GG者中位生存时间为21(17,24)m,明显长于CC者,差异有统计学意义(P<0.05);COX回归分析显示,携带rs4143185突变基因者可以获得较好的预后(HR<1,P<0.05).结论 检测外周血PD-L1基因多态性可能有助于筛选HCC高危人群中的高危人群,并可能对预测患者预后有帮助.