FOSB、SPP1基因表达对经肝动脉介入化疗栓塞术治疗的中晚期肝癌生存期预测价值

Predictive value of FOSB and SPP 1 gene expression on survival ofintermediate to advanced hepatocellular carcinoma treated withtranshepatic arterial interventional chemoembolization

目的探讨骨肉瘤原癌基凶同源物B(FOSB)、分泌性磷蛋白1(SPP 1)基因表达对经肝动脉介入化疗栓塞术治疗的中晚期肝癌患者术后生存期的预测价值。方法回顾性分析2016年1月—2017年10月在西安医学院第一附属医院进行诊治的中晚期肝癌患者115例作为研究对象,根据FOSB、SPP 1基因表达水平分为FOSB高表达组(n=52)、FOSB低表达组(n=63)及SPP 1高表达组(n=89)、SPP 1低表达组(n=26)。同时选取115例健康体检者为健康对照组。分析FOSB、SPP 1表达与中晚期肝癌患者临床病理特征的关系。对纳入研究的患者进行为期60个月的随访,Logistics风险回归模型分析影响患者生存期的危险因素。Kaplan-Meier生存曲线分析FOSB、SPP 1表达水平与患者生存预后的关系。结果肝癌患者外周血单个核细胞中FOSB mRNA表达水平明显低于健康对照组,SPP 1 mRNA表达水平明显高于健康对照组,差异具有统计学意义(P<0.05)。FOSB、SPP 1表达在中晚期肝癌患者肿瘤大小、Child-Pugh分级、淋巴转移、BCLC分期方面比较差异具有统计学意义(P<0.05)。单因素分析结果显示,存活组和死亡组在肿瘤大小、Child-Pugh分级、淋巴转移、BCLC分期、FOSB、SPP 1表达方面比较,差异均具有统计学意义(P<0.05)。肿瘤大小、Child-Pugh分级、淋巴转移、BCLC分期、FOSB低表达、SPP 1高表达均为中晚期肝癌患者生存期的独立危险因素(P<0.05)。随访时间60个月,患者生存率为17.39%(20/115),FOSB高表达组中位生存时间为39.7个月,明显高于FOSB低表达组的19.3个月(P<0.05);SPP 1低表达组中位生存时间为40个月,明显高于SPP 1高表达组的18个月(P<0.05)。结论FOSB在中晚期肝癌患者中表达明显下调,SPP 1表达上调,其对预测中晚期肝癌患者肝动脉介入化疗栓塞术治疗生存期具有一定的价值。FOSB、SPP 1有望成为评估介入术治疗患者预后的潜在指标,可协同肿瘤大小、Child-Pugh分级、淋巴转移、BCLC分期等临床指标预测或评估肝癌患者术后生存情况。

Objective To analyze the expression level of osteosarcoma proto-oncogene B(FOSB)and secretory phosphoprotein 1(SPP1)in liver cancer tissues of patients with advanced liver cancer treated by transcatheter arterial chemoembolization.Methods A retrospective analysis was performed on 115 patients with advanced liver cancer diagnosed and treated in the First Affiliated Hospital of Xi′an Medical University in Shanxi Province from January 2016 to October 2017.According to the level of FOSB and SPP 1 gene expression,they were divided into 52 cases of FOSB high expression group,63 cases of FOSB low expression group,89 cases of SPP 1 high expression group and 26 cases of SPP 1 low expression group.To analyze the relationship between the expression of FOSB and SPP 1 and the clinicopathological characteristics of patients with advanced hepatocellular carcinoma,the patients included in the study were followed up for 60 months.Logistic risk regression model was used to analyze the risk factors affecting the survival period of patients.Kaplan-Meier survival curve was used to analyze the relationship between the expression level of FOSB and SPP 1 and the survival and prognosis of patients.Results The expression level of FOSB mRNA in peripheral blood mononuclear cells of patients with liver cancer was significantly lower than that of the healthy control group,and the expression level of SPP 1 mRNA was significantly higher than that of the healthy control group(P<0.05).The expression of FOSB and SPP 1 was significantly different in tumor size,Child-Pugh grade,lymph node metastasis and BCLC stage in patients with advanced hepatocellular carcinoma(P<0.05).The results of univariate analysis showed that there were statistically significant differences between the survival group and the death group in tumor size,Child-Pugh grade,lymph node metastasis,BCLC stage,FOSB and SPP 1 expression(P<0.05).Tumor size,Child-Pugh grade,lymph node metastasis,BCLC stage,low expression of FOSB and high expression of SPP1 were all independent risk factors for survival of patients with advanced hepatocellular carcinoma(P<0.05).The follow-up time was 60 months.The survival rate of patients was 17.39%(20/115).The median survival time of FOSB high expression group was 39.7 months,which was significantly higher than 19.3 months of FOSB low expression group(P<0.05).And the median survival time of the low-expression SPP 1 group was 48 months.It was significantly higher than that in SPP 1 high expression group at 37.5 months(P<0.05).Conclusion The expression level of FOSB is significantly down-regulated and the expression of SPP1 is up-regulated in patients with advanced liver cancer,which has certain value in predicting the survival period of patients with advanced liver cancer treated by transcatheter arterial chemoembolization.FOSB and SPP 1 are expected to become potential indicators to evaluate the prognosis of patients undergoing interventional therapy,and can predict or evaluate the survival of patients with liver cancer after surgery in cooperation with clinical indicators such as Child-Pugh grade,lymph node metastasis,BCLC stage.