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目的 探索肌动蛋白结合蛋白(ANLN)在肝细胞肝癌(HCC)组织中的表达,分析ANLN对HCC肝移植受者术后远期存活的临床意义.方法严 格选择92例因HCC接受肝移植的受者,采用免疫组织化学法检测HCC组织以及癌旁非肿瘤(NT)肝组织中ANLN的表达水平,通过对肿瘤基因组图谱(TCGA)数据库RNA-seq数据分析HCC组织和NT肝组织中ANLN mRNA的表达水平,采用卡方检验和t检验分析ANLN表达与受者临床病理特征间的相关性,采用Log-rank检验和Cox回归模型分析ANLN表达对HCC肝移植受者术后远期存活的影响.结果 ANLN在HCC组织中的阳性表达率为37.0％ (34/92),明显高于NT肝组织的6.5％(6/92) (P＜0.001,(x2 =25.044);HCC组织ANLN mRNA的表达水平显著高于NT肝组织(P＜0.000 1).ANLN阳性表达与受者术前血清甲胎蛋白(AFP)水平＞400 μg/L(P＜0.001,x2=11.952)及肿瘤直径＞8 cm(P =0.034,x2=4.506)呈正相关;ANLN阳性表达(P=0.031,优势比=1.965,95％可信区间1.064～3.630)、肿瘤直径＞8 cm(P=0.003,优势比=2.841,95％可信区间1.437～5.617)、肿瘤分化不良(P=0.001,优势比=3.613,95％可信区间=1.646～7.928)、脉管癌栓(P=0.041,优势比=1.896,95％可信区间=1.028～3.498)和肿瘤发生坏死或出血(P=0.010,优势比=2.195,95％可信区间=1.211～3.979)是影响HCC肝移植受者术后5年累积存活率的独立危险因素.结论 HCC组织中ANLN表达水平上调,其阳性表达预示着HCC肝移植受者术后远期存活不佳.

Objective To explore the expression of ANLN in HCC and study the clinical value of ANLN expression for HCC patients after liver transplantation.Methods The protein and mRNA expression of ANLN was detected by immunohistochemistry and RNA-seq from TCGA respectively.Chi-square test and t test were used for correlation analysis between ANLN expression and clinicopathological characteristics.The predictive value of ANLN expression for HCC patients after liver transplantation was estimated by log-rank test and cox proportional hazards regression model.Results The positive protein expression rate of ANLN in HCC detected by immunohistochemistry was 37.0％ (34/92),significantly higher than 6.5 ％ (6/92) in para-carcinoma non-tumor tissue (P＜0.001,x2 =25.044).Upregulation of ANLN mRNA expression in HCC was also detected by the analysis of RNA-seq from the TCGA (P ＜ 0.000 1).The positive ANLN protein expression was positively correlated with AFP＞400 ng/L (P＜0.001,x2 =11.952) and tumor size ＞8 cm (P =0.034,x2 =4.506).The independent risk factors for poorer 5-year survival of patients after liver transplantation were confirmed,including positive ANLN protein expression (P =0.031,OR =1.965,95 ％CI =1.064-3.630),tumor size ＞8 em (P =0.003,OR =2.841,95 ％CI =1.437-5.617),worse differentiation degree (P =0.001,OR =3.613,95％ CI =1.646-7.928),peritumor intravascular cancer emboli (P =0.041,OR =1.896,95％CI =1.028-3.498) and tumor necrosis or hemorrhage (P=0.010,OR=2.195,95 ％CI=1.211-3.979).Conclusion The expression of ANLN in HCC is upregulated and the positive protein expression indicates the poor prognosis for long-term survival of patients after liver transplantation.