KIF21B在肝细胞癌中的表达及临床意义的研究

Expression of KIF21B in hepatocellular carcinoma and its clinical significance

背景与目的:驱动蛋白家族(kinesin superfamily,KIF)是一类调控微管运动的分子马达,参与细胞运动、有丝分裂、细胞内运输及癌变过程。KIF21B作为经典的驱动蛋白分子,同时也是微管系统动态平衡的调控子,其在肿瘤中的表达尚未见报道。探讨KIF21B在肝细胞癌(hepatocellular carcinoma,HCC)中的表达水平与HCC患者临床病理学特征的关系及对预后的影响。方法:通过癌症基因组图谱(The Cancer Genome Atlas,TCGA)分析KIF21B在HCC组织及正常组织中的表达差异,及其与临床病理学特征的关系;应用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检测2株HCC细胞及1株正常肝细胞中KIF21B的表达差异;应用免疫组织化学法检测于甘肃省人民医院2014年3月-2018年6月行HCC手术切除的116例HCC组织及其癌旁组织中KIF21B的表达差异,验证TCGA数据库结果,分析KIF21B表达水平与临床病理学特征之间的关系;应用COX回归模型及Kaplan-Meier法分析KIF21B表达对HCC患者预后的影响。结果:KIF21B在HCC组织的表达显著高于正常组织(P<0.01),此结果与TCGA数据库结果一致,与TNM分期、乙肝病毒感染和血管侵犯有关(P<0.05);KIF21B在2株HCC细胞中的表达明显高于正常肝细胞(P<0.05);Kaplan-Meier法分析显示,KIF21B高表达组5年生存率明显低于低表达组(P<0.05);COX分析显示,KIF21B是影响HCC预后的独立因素。结论:KIF21B在HCC组织中的表达明显高于正常组织,且与预后不良密切相关,可能参与HCC的发生、发展过程。

Background and purpose: Kinesin superfamily(KIF) is a group of classic molecular motors that regulate microtubule movement and participate in cell motility, mitosis, intracellular transportation and carcinogenesis. KIF21 B, a member of KIF and the regulator of microtubule dynamic system, has not been reported in tumor. The study aimed to investigate the correlation between KIF21 B expression in hepatocellular carcinoma(HCC) and the pathological features of patients with HCC, and its effect on prognosis. Methods: Data on the differential expression of KIF21 B in patients with HCC from The Cancer Genome Atlas(TCGA) database were analyzed. Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR) was used to detect the KIF21 B mRNA expression in HCC cell lines and hepatocyte lines. To validate the TCGA database results, immunohistochemical analysis was used to evaluate the differential expression of KIF21 B in HCC tissues and tumor adjacent tissues from 116 patients with HCC who underwent surgery in Gansu Provincial Hospital from March 2014 to June 2018, and this study further investigated the correlation between KIF21 B expression and pathological features of the patient with HCC. The COX and Kaplan-Meier methods were used to assess prognostic significance. Results: Immunohistochemistry results were consistent with the TCGA analysis showing increased KIF21 B expression levels in HCC tissues compared with adjacent normal tissues, and the correlation between KIF21 B expression and TNM stage, hepatitis B surface antigen(HBsAg) and vascular invasion was obvious(P<0.05). The expression of KIF21 B was obviously higher in HCC cell lines compared with hepatocyte lines(P<0.01). Kaplan-Meier analysis showed that the 5-year survival rate was significantly higher in lower KIF21 B expression group compared with higher KIF21 B expression group(P<0.05). COX proportional hazards regression analysis showed that KIF21 B was an independent factor affecting the prognosis of HCC. Conclusion: KIF21 B expression is significantly higher in HCC tissues compared with normal adjacent tissues, which is closely related to prognosis, and may be involved in development of HCC.