肝细胞肝癌组织中WDR4和EIF2A的表达及临床预后价值

陶珊珊; 王竞; 黄桂春

doi:10.3969/j.issn.2096-3882.2024.02.006

肝细胞肝癌组织中WDR4和EIF2A的表达及临床预后价值

The expression and clinical prognostic value of WDR4 and EIF2A in hepatocellular carcinoma tissue

摘要

摘要: 目的探讨肝细胞肝癌(HCC)组织中WD重复结构域4 (WDR4)、真核翻译起始因子2A (EIF2A)的表达情况及临床预后意义。方法收集2019年1月—2020年1月南京大学医学院附属金陵医院收治的90例HCC患者的临床资料。利用R语言(4.2.1版本)分析癌症基因组图谱(TCGA)数据库下载的327对HCC癌组织和癌旁组织中WDR4 mRNA、EIF2A mRNA表达的转录组测序数据。免疫组织化学检测HCC癌组织、癌旁组织中WDR4、EIF2A表达。分析HCC癌组织WDR4、EIF2A表达与临床病理特征的关系。Kaplan-Meier法分析WDR4、EIF2A表达对HCC患者预后的影响。Cox回归模型分析HCC预后的影响因素。结果 HCC癌组织WDR4 mRNA、EIF2A mRNA表达高于癌旁组织,差异有统计学意义(P均＜0.05)。HCC癌组织中WDR4、EIF2A表达阳性率高于癌旁组织,差异有统计学意义(P均＜0.05)。HCC癌组织WDR4 mRNA与EIF2A mRNA表达呈正相关(r=0.404,P＜0.001)。HCC癌组织中WDR4蛋白与EIF2A蛋白表达呈正相关(r=0.667,P＜0.05)。肿瘤最大径＞5 cm、TNM分期Ⅲ期及浸润型HCC癌组织中WDR4、EIF2A阳性率分别高于肿瘤最大径≤5 cm、TNM分期Ⅰ—Ⅱ期及非浸润型癌组织,差异有统计学意义(P均＜0.05)。WDR4阳性组3年累积生存率明显低于WDR4阴性组,差异有统计学意义(P=0.016)。EIF2A阳性组3年累积生存率明显低于EIF2A阴性组,差异有统计学意义(P=0.022)。肿瘤TNM分期Ⅲ期、肿瘤最大径＞5cm、WDR4阳性、EIF2A阳性是HCC患者不良预后的独立危险因素。结论 HCC组织中WDR4、EIF2A表达升高,两者与HCC不良临床病理特征有关,是评估HCC预后的肿瘤标志物。

Abstract: Objective To discuss the expression and clinical prognostic significance of WD repeat domain 4 (WDR4) and eukaryotic translation initiation factor 2A (EIF2A) in hepatocellular carcinoma (HCC) tissue.Methods A total of 90 HCC patients who were admitted to Affiliated Jinling Hospital,Medical School of Nanjing Uiversity from January 2019 to January 2020 were selected and their clinical data were collected. R language (version 4.2.1) was used to analyze the transcriptome sequencing data of WDR4 mRNA and EIF2A mRNA in 327 pairs of HCC and adjacent tissues from the Cancer Genome Atlas (TCGA) database. The expression of WDR4 and EIF2A in both HCC and adjacent tissues was detected by immunohistochemistry. The relationship between the expression of WDR4 and EIF2A in HCC tissues and clinical pathological features was analyzed. Kaplan Meier method was used to analyze the effect of WDR4 and EIF2A expression on the prognosis of HCC patients. The influencing factors on the prognosis of HCC was analyzed by the Cox regression model.Results The levels of WDR4 mRNA and EIF2A mRNA in the HCC tissues were significantly higher than those in the adjacent tissues (P<0.05). The positive rates of WDR4 and EIF2A in the HCC tissues were remarkably higher than those in the adjacent tissues (P<0.05). The expression of WDR4 mRNA in the HCC tissues was positively correlated with EIF2A mRNA expression (r=0.404, P<0.001). A significant positive correlation was found between the expression of WDR4 and EIF2A protein in the HCC tissues (r=0.667, P＜0.05). Furthermore, the positive rates of WDR4 and EIF2A in HCC tissues with a maximum tumor diameter >5 cm, TNM stage III and invasive type were significantly higher than those with a maximum tumor diameter ≤5 cm, TNM stage I-II and non-invasive type (P<0.05). The WDR4 positive group showed a significantly lower cumulative 3-year survival rate than the WDR4 negative group (P=0.016), while the EIF2A positive group had a significantly lower cumulative 3-year survival rate than the EIF2A negative group (P=0.022). Tumor TNM stage III, tumor maximum diameter >5 cm, and positive WDR4 and EIF2A expression were the independent risk factors for the poor prognosis of HCC patients.Conclusions The increased expression of WDR4 and EIF2A in HCC tissues is associated with poor clinicopathological characteristics, which can serve as tumor markers for evaluating the prognosis of HCC.

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