基于生物信息学分析PRKCD在肝细胞癌组织中的表达及临床意义  

Expression and clinical significance of PRKCD in liver hepatocellular carcinoma analyzed based on bioinformatics

作　　者：胡连涛 邓文俊 孙跞 鹿士振 李学斌 黎楚豪 王绎博 王欣然 李玥[1,2] 王伟群 HU Lian-tao;DENG Wen-jun;SUN Luo;LU Shi-zhen;LI Xue-bing;LI Chu-hao;WANG Yi-bo;WANG Xin-ran;LI Yue;WANG Wei-qun(Basic Medical College,Jiamusi University,Jiamusi 154007,China;Key Laboratory of Microecology‑immune Regulatory Network and Related Diseases,Jiamusi 154007,China;First Affiliated Hospital,Jiamusi University,Jiamusi 154007,China)

机构地区：[1]佳木斯大学基础医学院,黑龙江佳木斯154007 [2]黑龙江省微生物-免疫调解网络与相关疾病重点实验室,黑龙江佳木斯1540073 [3]佳木斯大学第一临床医学院,黑龙江佳木斯154007

出　　处：《海南医学院学报》2022年第14期1088-1095,共8页Journal of Hainan Medical University

基　　金：黑龙江省属高等学校基本科研业务费优秀创新团队建设项目(2019-KYYWF-1334)。

摘　　要：目的:基于生物信息学分析蛋白激酶Cδ(PKCδ,PRKCD)在肝细胞癌组织中的表达及临床意义,以期为寻找肝细胞癌的临床诊疗潜在分子标志物和靶点提供参考。方法:利用TheCancerGenome Atlas(TCGA)和UCSCXena平台获取肝细胞癌和癌旁组织中PRKCD的mRNA表达量和临床数据,比较PRKCD mRNA在两组样本中的表达差异;利用HumanProteinAtlas数据库分析PRKCD蛋白在肝细胞癌和癌旁组织中的表达差异;利用TCGA分析PRKCD mRNA表达与肝细胞癌临床病理特征和预后的相关性;利用TCGA数据库对肝细胞癌中PRKCD表达进行GSEA富集分析,并从遗传和表观遗传学的观点分析PRKCD表达变化的原因。结果:PRKCD在肝细胞癌组织中的mRNA和蛋白质水平均显著高于癌旁组织;PRKCD表达与TNM分期、组织学级别、甲胎蛋白含量和患者生存状态相关,并且其表达水平具有一定的临床诊断准确性;Kaplan-Meier分析显示PRKCD低表达患者的预后显著优于高表达患者;单因素和多因素Cox回归分析显示,PRKCD是肝细胞癌患者独立预后因素,且TNM为Ⅲ和Ⅳ期生存曲线的风险比显著大于Ⅰ和Ⅱ期;GSEA分析显示PRKCD主要富集在细胞周期和DNA复制等过程,并与两者呈正相关性,且PRKCD主要参与了趋化因子、NOD样受体、PPAR、脂肪细胞因子和T细胞受体信号通路;遗传和表观遗传分析显示PRKCD表达水平与其基因的拷贝数呈正相关,但与其甲基化水平呈负相关。结论:PRKCD基因在肝细胞癌组织中表达上调,且其表达上调与患者预后不良具有显著相关性。Objective:To analyze the expression of protein kinase C delta(PKCδ,PRKCD)in liver hepatocellular carcinoma and its clinical significance based on bioinformatics methods,in order to provide a new evidence for the study of therapeutic targets for liver hepatocellular carcinoma.Methods:The PRKCD mRNA expression levels in liver hepatocellular carcinoma tissues and adjacent tissues were downloaded from the the Cancer Genome Atlas and UCSC Xena databases in order to analyze the difference.The protein expression of PRKCD in liver hepatocellular carcinoma and adjacent tissues was analyzed by Human Protein Atlas databases.Furthermore,the relationship between PRKCD mRNA expression level and the clinicopathological features and prognosis of patients with liver hepatocellular carcinoma was evaluated.GSEA enrichment analysis was carried out for PRKCD in liver hepatocellular carcinoma in order to explore the causes of changes in PRKCD expression from the perspective of genetic and epigenetics based on collected liver hepatocellular carcinoma data.Results:Both the mRNA and protein expression level of PRKCD in liver hepatocellular carcinoma tissues were significantly higher than those in the adjacent tissues.Its expression level was correlated with TNM stage,histologic grade,Alpha fetoprotein concentrations as well as the living status of the patients,showing certain clinical diagnostic accuracy.Kaplan-Meier analysis showed that the prognosis of patients with low PRKCD expression was significantly better than those with high PRKCD expression levels.Univariate and multivariate Cox regression analysis showed that PRKCD was an independent prognostic factor in patients with liver hepatocellular carcinoma,and it was also found that the risk ratio of TNM stageⅢand stageⅣsurvival curve(HR)was significantly greater than that of stageⅠand stageⅡ.GSEA analysis showed that PRKCD was enriched in cell cycles and DNA replication,which was positively correlated with each other.Enrichment analysis found that PRKCD was mainly involved i

关 键 词：蛋白激酶Cδ(PKCδ PRKCD) 肝细胞癌 生物信息学分析 预后 

分 类 号：R735.7[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]