HBV相关肝细胞肝癌微脉管癌栓局部免疫微环境对患者术后预后的影响

Effect of immune microenvironment of microvascular invasion on prognosis of patients with HBV-related hepatocellular carcinoma

目的:探讨HBV相关肝细胞肝癌(hepatocellular carcinoma,HCC)微脉管侵犯(microvascular invasion,MVI)癌栓局部免疫微环境对患者预后的影响。方法:入选2012年3月至2013年11月初诊HBV相关HCC患者。所有入选病例均有HBV感染史且无其他肝脏疾病基础,患者接受单纯手术治疗,术后均未接受介入、放化疗等其他治疗方案。所有病例均定期随访,末次随访至2018年11月30日,主要终点事件为术后HCC相关死亡或HCC复发,记录患者总生存期(overall survival,OS)及无复发生存期(relapse free survival,RFS)。根据术后病理结果将入选患者分为MVI组及无MVI组,采用单因素、多因素分析探讨MVI对患者预后的影响。进一步对MVI患者术后病理进行分析,采用数字病理切片定量分析癌栓T淋巴细胞、B淋巴细胞等免疫细胞数量,探讨癌栓局部免疫微环境对患者预后的影响。结果:共175例患者纳入研究,包括MVI组68例,无MVI组107例,截至随访终点有35例死亡、88例复发。单因素分析和多因素分析均显示,MVI是HCC患者术后RFS的危险因素(P<0.05)。ROC分析表明,MVI癌栓局部CD4+及CD8+T细胞对患者术后RFS具有预测价值(P=0.031、0.036),截断值分别为0.208、0.465。基于上述截断值分组后的生存分析结果表明,癌栓CD4+T和CD8+较高表达组患者术后RFS长于对应的较低表达组,差异有统计学意义(P<0.05)。结论:MVI是HBV相关HCC患者RFS重要且独立的影响因素,其癌栓内CD4+/CD8+T细胞数量可能与首发HCC患者术后复发风险负相关。

Objective:To evaluate the value of immune microenvironment of microvascular invasion in predicting HBV-related hepatocellular carcinoma(HCC)prognosis.Methods:A cohort of patients primarily diagnosed as HBV-related HCC between March 2012 and November 2013 were included.All patients had a history of HBV infection and no basis for other liver diseases,and were treated with simple surgery.No intervention,chemoradiotherapy and other treatment options were provided after surgery.Patients were followed up regularly,with the last follow-up until November 30th,2018.Both overall survival(OS)and relapse-free survival(RFS)were primary endpoint indexes.Patients were divided into MVI group and non-MVI group according to the postoperative pathology.Univariate and multivariate analysis were used to explore the effect of MVI on the prognosis of patients.Further,the postoperative pathology of patients with MVI was analyzed,and the digital pathological sections were used to quantitatively analyze the number of T,B lymphocytes and other immune cells in the local tissue of tuntor thrombi,to explore the effect of the local immune microenvironment of cancer thrombi on the prognosis of patients.Results:Totally,175 qualified patients(68 cases in MVI group and 107 cases in non-MVI group).By the end of follow-up,35 cases died and 88 cases recurred.Univariate/multivariate studies showed that the MVI in HBV-related HCC increased the risk of recurrence(P<0.05).ROC analysis showed that CD4 T cells or CD8T cells in tumor thrombi had predictive value for RFS of patients while their cutoffs were determined as 0.208 and 0.465,respectively.Based on the cutoffs,the survival analysis indicated that those MVI cases infiltrated with a higher number of CD4 T cells or CD8 T cells were correlated with a better RFS(P<0.05).Conclusions:Microvascular invasion is an independent RFS factor for HBV-related HCC.The number of CD4 or CD8 T cells in the tumor thrombi may be negatively correlated with the RFS risk of the primary HCC patients.