KIF4A在肝细胞癌中的表达及预后价值分析  

Expression of KIF4A in hepatocellular carcinoma and its prognostic value

作　　者：蓝祝晶 王继龙 王珏 易麒麟 王维[1] 黄柯豫 金宗睿 吴国林 朱海[1] 徐邦浩[1] 郭雅[1] 文张[1] LAN Zhujing;WANG Jilong;WANG Jue;YI Qiling;WANG Wei;HUANG Keyu;JIN Zongrui;WU Guolin;ZHU Hai;XU Banghao;GUO Ya;WEN Zhang(Department of Hepatobiliary Surgery,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院肝胆外科,广西南宁530021

出　　处：《中国普通外科杂志》2022年第1期55-63,共9页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(81902983);广西自然科学基金资助项目(2018JJB140382);广西医疗卫生适宜技术开发与推广应用基金资助项目(S2018100);广西医科大学第一附属医院“优秀医学英才”科研创新能力培养基金资助项目(180327)。

摘　　要：背景与目的:肝细胞癌(HCC)是原发性肝癌最常见的病理类型,其起病隐匿,预后较差,位居癌症相关死亡原因第3位。KIF4A在多种恶性肿瘤中呈高表达且与不良预后密切相关,然而其在HCC中的作用及机制尚不清楚。因此,本研究分析KIF4A基因在HCC中的表达情况及预后价值,并探讨相关的分子机制。方法:从癌症基因组图谱(TCGA)下载获取HCC相关的表达数据和临床参数,使用R语言和Perl包等软件分析KIF4A在正常肝组织、HCC组织中的表达水平及其与临床病理特征的关系。采用Kaplan-Meier生存分析方法和随时间变化的ROC曲线评估KIF4A在HCC中的预后价值;单因素和多因素Cox回归分析用于预测影响HCC患者预后的危险因素。纳入相关临床病理因素,使用R软件构建预测肝癌患者预后的列线图。采用免疫组化法验证KIF4A在HCC组织及其对应癌旁组织的临床标本中的表达水平;GSEA富集分析用于探讨KIF4A在HCC中可能调控的分子信号通路。结果:KIF4A在HCC组织中的表达水平明显高于正常肝组织(P<0.001),且KIF4A高表达患者的总体生存时间(OS)明显短于低表达患者(P=0.002),ROC曲线1、3、5年OS的曲线下面积(AUC)依次为0.783、0.662、0.574。肿瘤临床分期(HR=2.084,95%CI=1.590~2.733,P<0.001)、T分期(HR=1.980,95%CI=1.541~2.543,P<0.001)和KIF4A表达水平(HR=1.113,95%CI=1.062-1.167,P<0.001)与患者OS明显有关,且KIF4高表达(HR=1.089,95%CI=1.034-1.147,P=0.001)是HCC患者预后的独立危险因素。列线图结果显示KIF4A表达水平对总分值有显著影响,而其他临床病理因素对总评分的影响相对较小。免疫组织化学检测证实KIF4A在HCC组织中呈阳性表达,而在癌旁肝组织中呈弱阳性或阴性表达;GSEA富集分析结果提示KIF4A可能参与调控碱基切除修复、细胞周期、DNA复制、错配修复、m TOR信号通路、核酸切除修复、P53信号通路、癌症通路、磷脂酰肌醇信号传导等9条信号通�Background and Aims: Hepatocellular carcinoma(HCC) is the most prevalent primary liver cancer,with insidious onset and poor prognosis, and ranks the third leading cause of cancer-related deaths worldwide. KIF4 A is highly expressed in a variety of malignancies and strongly associated with poor prognosis. However, the role and mechanism underlying KIF4 A in HCC remain unclear. Therefore, this study was conducted to investigate the expression and prognostic value of KIF4 A in HCC, and the associated mechanism.Methods: The expression data and clinical parameters associated with HCC were obtained from the Cancer Genome Atlas(TCGA) and the expression levels of KIF4 A in HCC and its relationship with clinicopathologic features were analyzed using software such as R language and Perl package. The prognostic value of KIF4 A in HCC was evaluated by the Kaplan-Meier survival analysis and timedependent ROC curves. The independent risk factors for the prognosis of HCC patients were determined by univariate and multivariate Cox regression analysis. A nomogram for predicting the prognosis of HCC patients was constructed by including relevant clinicopathologic factors using R software.Immunohistochemical staining was performed to verify the expression levels of KIF4 A in the clinical specimens of HCC tissues and their adjacent noncancerous tissues. The molecular signaling pathways potentially regulated by KIF4 A in HCC were analyzed by GSEA enrichment analysis.Results: The expression level of KIF4 A in HCC tissues was significantly higher than that in normal liver tissues(P<0.001). The overall survival(OS) time of patients with high KIF4 A expression was shorter than that of those with low KIF4 A expression(P=0.002), and the area under curve(AUC) of ROC curves for the 1-, 3-, and 5-year OS were 0.783, 0.662 and 0.574, respectively. The clinical stage(HR=2.084, 95% CI=1.590-2.733,P<0.001), T stage(HR=1.980, 95% CI=1.541-2.543,P<0.001) and KIF4 A expression level(HR=1.113, 95% CI=1.062-1.167,P<0.001) were significantly associated

关 键 词：癌 肝细胞 驱动蛋白 预后 计算生物学 

分 类 号：R735.7[医药卫生—肿瘤]