CSMD1基因rs1613815基因型与肝细胞肝癌临床病理特征的关系

Association of rs1613815genotypes in CSMD1gene with clinicopathological parameters of hepatocellular carcinoma

目的探讨肝细胞肝癌患者中CSMD1基因rs1613815基因型与临床病理特征的关系。方法选取2009年1—7月复旦大学附属中山医院肝外科收治的经病理确诊的肝细胞癌(hepatocellular carcinoma,HCC)患者146例,收集患者的临床和病理资料。根据我们前期预实验研究结果,采用美国Sequenom公司建立的MassARRAY检测平台分析CSMD1基因rs1613815位点的各种基因型,回顾性分析其与HCC患者临床病理资料的关系。Kaplan-Meier法和COX回归模型用于评估其预后价值。结果在146例HCC标本中,rs1613815位点AA、AC和CC基因型分别有33例、49例和64例。其中在中晚期HCC患者中,携带AC/CC基因型的患者其癌栓(含肉眼癌栓和镜下癌栓)发生率明显高于携带AA基因型的患者(70.6%vs.36.4%),差异具有统计学意义(P=0.039);携带AC/CC基因型的患者处于T2-4N0M0期的比例明显高于携带AA基因型的患者(59.8%vs.31.2%),差异同样具有统计学意义(P=0.004)。而在年龄、性别、HbsAg、肿瘤直径和数目及血清甲胎蛋白(alpha-fetoprotion,AFP)水平等分组中,AC/CC基因型和AA基因型所占的比例之间差异无统计学意义(P>0.05)。在肿瘤直径≥5 cm的患者中,携带AA基因型的患者术后总生存率和无瘤生存率明显高于携带AC/CC基因型的患者(P值分别为0.023和0.005)。结论 CSMD1基因rs1613815多态性与肝细胞肝癌患者的癌栓形成和TNM分期较晚密切相关,提示其具有较高的转移潜能和不良预后。

Objective To investigate the relationship between rs1613815 genotypes in CSMD1 gene with clinicopathological parameters of hepatocellular carcinoma（HCC）patients. Methods From Jan.to Jul.in2009,146 pathologically confirmed HCC patients were enrolled from Department of Liver Surgery,Zhongshan Hospital,Fudan University.We collected the clinical and pathological data.The polymorphism of CSMD1 gene（rs1613815）was detected by USA Sequenom MassARRAY.According to the results of our previous pre-experiment,the relationship between different genotypes of rs1613815 and clinicopathological parameters of those HCC patients was analyzed retrospectively.Kaplan-Meier method and Cox regression model were used to estimate clinical outcomes. Results In the 146 cases of HCC,we found 33 cases carrying AA genotype,49 carrying AC genotype and 64 carrying CC genotype in rs1613815.In mid-advanced HCC patients,the incidence rate of tumor thrombi（including macroscopic and microscopic thrombi）in those patients carrying AC/CC genotype was apparently higher than those carrying AA genotype（70.6%vs.36.4%）,and the difference was statistically significant（P=0.039）.Meanwhile,the ratio of carring AC/CC genotype patients in T2-4N0M0 was also significantly higher than those carrying AA genotype（59.8%vs.31.2%,P=0.004）.No significant difference was found between AC/CC and AA genotype in age,gender,HbsAg,tumor size and number,serum alpha-fetoprotein（AFP）level and other clinicopathological parameters（P〉0.05）.In patients with tumor size≥5 cm,the AA group had a significantly higher overall survival rate or recurrence-free survival rate than the AC/CC group（the Pvalue was 0.023 and 0.005,respectively）. ConclusionsCSMD1 rs1613815 polymorphisms were positively correlated with tumor thrombi status and advanced TNM-stage of HCC,which indicated that it had a high potential of metastasis and poor prognosis.