肝细胞癌复发前后干细胞性标志物的变化特征及其与临床病理特征的关系

The expression change of stemness-related markers in recurrent hepatocellular carcinoma and relationship with clinicopathologic characteristics

目的探讨肝细胞癌复发前后干细胞性标志物的变化特点及其与临床病理特征的关系。方法回顾性收集四川省肿瘤医院2010年1月至2018年10月期间收治的先后进行初次肝癌切除和复发后再次切除的25例肝细胞癌患者的病理切片;通过免疫组织化学染色检测表皮细胞黏附分子(EpCAM)、CD133、CD90和CD1174种干细胞性标志物的表达,采用原位荧光杂交方法检测端粒长度。结果肝细胞癌复发前的PLT计数和肿瘤直径均高于(大于)复发后,且肿瘤多发和微血管癌栓(MVI)占比较低,端粒长度较短(P<0.05),但肝细胞癌复发前后组织中CD90、CD133、CD117和EpCAM的表达水平比较差异均无统计学意义(P>0.05)。肿瘤直径、肿瘤数量、巴塞罗那分期(BCLC分期)、卫星结节以及分化程度均不影响CD90、CD133、CD117和EpCAM的表达(P>0.05);但对于MVI阳性的肿瘤,其EpCAM表达水平(P=0.016)和端粒长度(P=0.001)均高于MVI阴性的患者;同时直径<5 cm的肿瘤(P=0.038)和低分化(P=0.046)的肿瘤其端粒长度也更长。相关分析发现,端粒长度与EpCAM(r=-0.092,P=0.513)、CD90(r=-0.235,P=0.100)、CD133(r=0.024,P=0.867)和CD117(r=-0.277,P=0.052)的表达水平均没有相关性;但EpCAM与CD133呈正相关(r=0.358,P=0.011)。生存分析发现,BCLC B~C分期(P=0.040)和低分化程度(P=0.003)是影响肝细胞癌患者首次切除后无瘤生存的危险因素;BCLC B~C分期(P=0.017)和肿瘤直径>5 cm(P=0.035)是影响复发后无瘤生存的危险因素。结论肝细胞癌复发前后具有相似的干细胞性标志物表达特征,但复发性肝癌具有更长的端粒长度;EpCAM表达水平和端粒长度与MVI相关。

Objective To investigate the expression change characteristic of stemness-related markers for recurrent hepatocellular carcinoma(HCC),and to discuss the relationship between stemness-related markers and clinicopathologic characteristics of HCC.Methods We collected 25 recurrent HCC patients who also had the first liver resection for HCC in Sichuan Cancer Hospital from Jan.2010 to Oct.2018.Immunohistochemistry was used to compare expressions of CD133,CD90,CD117,and epithelial cell adhesion molecule(EpCAM)in HCC tissues.Fluorescence in situ hybridization was used to detect telomere length.Results The primary HCC had higher platelet count,larger tumor,less microvascular invasion(MVI),and less multiple HCC than the recurrent HCC(P<0.05),but the expressions of CD90,CD133,CD117,and EpCAM were not significantly differed after recurrence(P>0.05).The expressions of CD90,CD133,CD117,and EpCAM were not associated with tumor size,tumor number,Barcelona Clinic Liver Cancer Staging(BCLC staging),satellite nodules,and differentiation(P>0.05).The MVI-positive group had a significantly higher expression level of EpCAM(P=0.016)and longer telomere length(P=0.001).The telomere length was longer for tumors diameter less than5 cm(P=0.038)and poor differentiation(P=0.046).Correlation analysis found that there was no relationship between telomere length and expression levels of EpCAM(r=-0.092,P=0.513),CD90(r=-0.235,P=0.100),CD133(r=0.024,P=0.867),and CD117(r=-0.277,P=0.052),but an apparent positive correlation between expression levels of EpCAM and CD133 was found(r=0.358,P=0.011).Survival analysis found that poor differentiation(P=0.003)and BCLC B-C staging(P=0.040)were the risk factors of disease-free survival for patients after first HCC resection,and BCLC B-C staging(P=0.017)and tumor diameter more than 5 cm(P=0.035)were the risk factors for recurrent HCC.Conclusions Recurrent HCC had similar stemness-related markers expression and longer telomere length.Expression level of EpCAM and telomere length were associated with MVI.