[Significance of expression of Myc-induced nuclear antigen 53 in hepatocellular carcinoma and its relationship with patient prognosis]

Zhonghua Gan Zang Bing Za Zhi. 2020 Mar 20;28(3):259-265. doi: 10.3760/cma.j.cn50113-20191104-00405.
[Article in Chinese]

Abstract

Objective: To detect the expression of Myc-induced nuclear antigen 53 (Mina53) and liver tissue >5 cm from the edge of the tumor (LTM5), and analyze its relationship with tumorigenesis, clinicopathological characteristics, and patient survival and prognosis in hepatocellular carcinoma (HCC). Methods: The expression levels of Mina53 mRNA and protein in 18 pairs of fresh HCC and LTM5 were assessed by qRT-PCR and Western blot, respectively. The expression of Mina53 in 284 pairs of HCC and LTM5 sample was determined by immunohistochemistry. Paired-sample t-test was used for the comparison of measurement data among groups, and heterogeneity of variance was tested using Wilcoxon rank-sum test. χ (2) test was used for the comparison of measurement data among groups. Kaplan-Meier method and log-rank test were used for survival analysis. Cox regression model was used for single factor and multi factor analysis. Results: The relative expression levels of Mina53 mRNA and protein in 18 fresh HCC tissues were significantly higher than those in LTM5 tissues (mRNA: -4.41 ± 1.48 and -5.93 ± 1.65, t = 3.100, P = 0.007; protein: 1.12 ± 0.29 and 0.46 ± 0.21, t = 10.616, P < 0.001). The relative expression level of Mina53 in 284 HCC tissues was higher than that of LTM5 (z = -18.739, P < 0.001). The expression level of Mina53 was associated with tumor size (χ (2) = 5.474, P = 0.019), vascular invasion (χ (2) = 8.965, P = 0.003), pathological grade (χ (2) = 12.006, P = 0.002), and TNM stage (χ (2) = 16.686, P < 0.001). The overall postoperative survival time and disease-free survival time of patients with high expression of Mina53 (28.5 months and 22.7 months, respectively) were shorter than those with low expression (33.0 months and 31.8 months, respectively) (P < 0.05) in HCC. Cox multivariate regression analysis showed that Mina53 and multiple tumors were independent prognostic factors affecting the overall postoperative survival time and disease-free survival time of HCC patients (P < 0.05). Conclusion: Mina53 may play an important role in the occurrence of HCC and participate in the process of tumor growth as well as invasion and metastasis. The high expression of Mina53 signifies that the patient has a poor prognosis and thus can be used as a potential marker for judging the prognosis of HCC patients.

目的: 检测Myc诱导的核抗原53(Mina53)在肝细胞肝癌(HCC)及距肿瘤边缘>5 cm的肝组织(LTM5)中的表达,并分析其与肿瘤发生、临床病理特征及患者生存预后的关系。 方法: 用实时荧光定量多聚核苷酸链式反应(qRT-PCR)和蛋白质印迹法(Western blot)分别检测18对新鲜HCC及LTM5中Mina53 mRNA和蛋白质的表达水平;用免疫组织化学方法检测Mina53在284份HCC及LTM5标本中的表达。计量资料组间比较采用配对样本t检验,方差不齐的数据采用Wilcoxon秩和检验;计数资料组间比较采用χ(2)检验;Kaplan-Meier法、Log- Rank检验进行生存分析;Cox回归模型进行单因素、多因素分析。 结果: 18对新鲜HCC组织中Mina53 mRNA和蛋白质的相对表达水平均明显高于其LTM5组织(mRNA:-4.41±1.48与-5.93±1.65,t = 3.100,P = 0.007;蛋白质:1.12±0.29与0.46±0.21,t = 10.616,P < 0.001);Mina53在284份HCC组织中的相对表达水平高于LTM5(z = -18.739,P < 0.001)。Mina53的表达水平与肿瘤大小(χ(2) = 5.474,P = 0.019)、脉管侵犯(χ(2) = 8.965,P = 0.003)、病理分级(χ(2) = 12.006,P = 0.002)、TNM分期(χ(2) = 16.686,P < 0.001)有关;Mina53高表达HCC患者的术后总体生存时间和无病生存时间(分别为28.5个月、22.7个月)较低表达者(33.0个月、31.8个月)更短(P值均< 0.05);Cox多因素回归分析表明,Mina53及肿瘤多发性是影响HCC患者术后总体生存时间和无病生存时间的独立预后因素(P值均<0.05)。 结论: Mina53可能在HCC发生中起重要作用,并参与肿瘤生长及浸润转移过程;Mina53高表达提示患者预后不良,可作为判断HCC患者预后的潜在标志物。.

Keywords: Carcinoma, hepatocellular; Myc-induced nuclear antigen 53; Neoplasm metastasis; Prognosis.

MeSH terms

  • Antigens, Nuclear
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Dioxygenases / genetics*
  • Histone Demethylases / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Neoplasm Staging
  • Nuclear Proteins / genetics*
  • Prognosis

Substances

  • Antigens, Nuclear
  • Biomarkers, Tumor
  • Nuclear Proteins
  • Dioxygenases
  • Histone Demethylases
  • RIOX2 protein, human