ANLN、CYP2C9、HMMR在乙型肝炎病毒相关肝细胞癌中的表达及其对预后的影响

摘要/Abstract

摘要： 目的研究肌动蛋白结合蛋白(ANLN)、细胞色素P450(Cytochromes P 450,CYPs)亚家族成员CYP2C9、透明质酸介导运动因子受体(HMMR)在乙型肝炎病毒相关肝细胞癌(HBV-HCC)组织中的表达及对其预后的影响。方法收集手术切除的25份HCC标本。采用免疫组织化学方法分析ANLN、CYP2C9、HMMR蛋白表达水平在癌组织及癌旁组织的差别,采用Log-Rank检验评估三者对HCC患者术后复发及远期存活的影响。结果 HCC患者癌组织的ANLN、CYP2C9免疫反应性评分(IRS)低于癌旁组织分别为(2.4±2.5)分比(3.7±2.7)分(t=2.18,P=0.039)和(4.2±2.8)分比(8.6±1.4)分(t=6.21,P<0.01),癌组织中的HMMR IRS高于癌旁组织为8.0(4.0,8.0)分比4.0(2.5,4.0)分(Z=3.94,P<0.01)。但不同ANLN、CYP2C9、HMMR蛋白表达水平对HCC患者术后复发时间及5年存活率影响差异无统计学意义(中位复发时间高水平比低水平:ANLN 38.6月比33.3月,CYP2C9 36.5月比35.5月,HMMR 33.1月比41.3月;中位生存时间高水平比低水平:ANLN 56.3月比51.1月,CYP2C9 55.1月比51.5月,HMMR 53.0月比55.2月;均P>0.05)。多因素Cox回归分析提示,BCLC、家族史对术后复发时间的影响差异有统计学意义(HR=2.435,P=0.025;HR=0.165,P=0.009),AFP、家族史与术后5年存活率独立相关(HR=229.488,P=0.041;HR=0.054,P=0.014)。结论 ANLN、CYP2C9、HMMR蛋白表达水平在HCC患者癌组织及癌旁组织存在差异,但对预后未产生影响,提示其可作为HCC诊断的潜在标志物。

关键词: 肝细胞癌, ANLN, CYP2C9, HMMR, 预后

Abstract: Objective To investigate the expression of actin binding protein (ANLN), Cytochromes P450 (CYPs) subfamily members CYP2C9 and hyaluronic acid mediated movement factor receptor (HMMR) in hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) tissues and the effects on the prognosis of HCC patients. Methods Samples of 25 surgically resected HCC patients were collected, and immunohistochemistry was used to analyze the differences in the protein expression levels of ANLN, CYP2C9 and HMMR in tumor tissues and adjacent tissues, as well as the effects on postoperative recurrence and long-term survival of HCC patients were evaluated by log-rank test. Results The Immunoreactivity scoring system (IRS) of ANLN and CYP2C9 in tumor tissues of HCC patients were lower than those in adjacent tissues (ANLN:2.4±2.5 vs.3.7±2.7, t=2.18, P=0.039;CYP2C9:4.2±2.8 vs. 8.6±1.4, t=6.21, P<0.001), but the IRS of HMMR in tumor tissues was higher than that in adjacent tissues (8.0 (4.0, 8.0) vs. 4.0 (2.5, 4.0), Z=3.94, P<0.001). However, different protein expression levels of ANLN, CYP2C9 and HMMR had no significant difference in postoperative recurrence time and 5-year survival rate of HCC patients(Disease-free survival high vs. low:ANLN 38.6m vs.33.3 m, CYP2C9 36.5 m vs.35.5 m, HMMR 33.1 m vs.41.3 m;5-year overall survival high vs. low:ANLN 56.3 m vs.51.1 m, CYP2C9 55.1 m vs.51.5 m, HMMR 53.0 m vs.55.2 m;P>0.05). Multivariate Cox regression analysis showed that the influence of BCLC and family history on postoperative recurrence time was statistically different (HR=2.435, P=0.025;HR=0.165, P=0.009). AFP and family history were independently associated with 5-year survival rate in HCC patients (HR=229.488, P=0.041;HR=0.054, P=0.014). Conclusion The protein expression levels of ANLN, CYP2C9 and HMMR were different in HCC tumor and adjacent tissues. It suggested that they could be used as potential markers for the diagnosis of HCC.

Key words: Hepatocellular carcinoma, ANLN, CYP2C9, HMMR, prognosis

黄倩, 李亚楠, 曾达武. ANLN、CYP2C9、HMMR在乙型肝炎病毒相关肝细胞癌中的表达及其对预后的影响[J]. 肝脏, 2023, 28(7): 775-780.

HUANG Qian, LI Ya-nan, ZENG Da-wu. Expression and prognostic value of ANLN, CYP2C9 and HMMR in hepatitis B virus-associated hepatocellular carcinoma[J]. Chinese Hepatolgy, 2023, 28(7): 775-780.

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