基于癌症多组学数据库深度解析磷酸甘油激酶1在肝细胞癌中的表达及临床意义  

Expression and clinical significance of phosphoglycerate kinase 1 in hepatocellular carcinoma based on bioinformatics methods

作　　者：管成剑 于华婧 张小东 饶全 张伟涛 刘坤 吴鸿伟[1] 汪栋[1] 张忠涛[1] 郭伟[1] GUAN Cheng-jian;YU Hua-jing;ZHANG Xiao-dong;RAO Quan;ZHANG Wei-tao;LIU Kun;WU Hong-wei;WANG Dong;ZHANG Zhong-tao;GUO Wei(Department of General Surgery,Beijing Friendship Hospital,Capital Medical University&National Clinical Research Center for Digestive Diseases,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院普通外科,国家消化系统疾病临床医学研究中心,北京100050

出　　处：《解剖学报》2022年第6期744-753,共10页Acta Anatomica Sinica

基　　金：国家自然科学基金(82103484);北京市自然科学基金(7214218);北京市教育委员会科技计划一般项目(KM202110025015)。

摘　　要：目的 探讨磷酸甘油激酶1 (PGK1)在肝细胞癌(HCC)发生中的作用以及其潜在的蛋白质翻译后修饰位点,为PGK1作为肝癌诊断生物标志物和防控靶点提供依据。方法 以泛癌的角度,从癌症基因组数据库TCGA中获取10 967份样本资料,利用cBioPortal和UALCAN肿瘤基因分析工具,探讨PGK1基因在不同肿瘤中的表达情况和预后改变,随后将目标聚焦在肝细胞癌中,分析PGK1在肝肿瘤组织和正常组织间的表达差异;从GEO数据库获取肝癌患者的样本数据,分析PGK1在诱发肝细胞癌发生发展中的潜在作用;同时,通过Real-time PCR、Western blotting实验等从mRNA、蛋白水平分析PGK1在肝细胞癌和癌旁组织中的表达差异,并进行细胞侵袭、增殖实验的功能验证;通过String数据库检索PGK1相关蛋白并进行功能富集分析;最后采用CSS-Palm数据库和生物信息学方法预测PGK1上的蛋白质翻译后修饰位点。结果 PGK1基因在包括肝细胞癌在内的多种实体瘤中异常扩增和过度表达,且PGK1的高表达与肝细胞癌的不良预后相关。PGK1多个位点上存在多种新型表观遗传修饰位点。结论 PGK1与包括肝癌在内的多种癌症的发生发展及糖酵解代谢异常密切相关,表观遗传修饰能够调控PGK1并影响其细胞功能。Objective To investigate the role of phosphoglycerate kinase 1(PGK1) in tumorigenesis and its potential post-translational modification sites were investigated by bioinformatics method and molecular biology experimental techniques, in order to provide evidence for PGK1 as a hepatocellular carcinoma(HCC) diagnostic biomarker and therapeutic target. Methods From pan-cancer’s point of view, 10 967 samples were obtained from the cancer genome database TCGAs, and the expression of PGK1 in different tumors was explored by using cBioPortal and UALCAN analysis tools;Focusing on HCC, the expression differences of PGK1 in hepatocellular carcinoma tumor tissues and normal tissues were further analyzed by using GEO database analysis, Real-time PCR, Western blotting and cell invasion assay;The String database was used to analyze the protein-protein interaction network and gene set enrichment analysis;The CSS-Palm database and bioinformatics method were used to predict protein post-translational modification sites on PGK1. Results The PGK1 gene was abnormally amplified and overexpressed in various solid tumors, including hepatocellular carcinoma, and overexpression of PGK1 was correlated with a poor prognosis in hepatocellular carcinoma. Multiple novel post-translational modifications were existed on PGK1. Conclusion PGK1 is closely related to the occurrence and development of various cancers including HCC and glycolytic metabolism abnormalities. Epigenetic modifications can regulate PGK1 and affect its cellular function in HCC.

关 键 词：磷酸甘油激酶1 癌症 肝细胞癌 生物信息学 糖酵解 预后 免疫印迹法 人 

分 类 号：R735.7[医药卫生—肿瘤]