PPP1R105基因在肝细胞癌中的表达相关信号通路及其与患者预后关系  

Clinical significance of expression of PPP1R105 in hepatocellular carcinoma

作　　者：孙建贺 侯计平[1] 康永振 Jian-He Sun;Ji-Ping Hou;Yong-Zhen Kang(Department of Hepatobiliary Surgery,People’s Hospital of Baodi District,Tianjin 301800,China)

机构地区：[1]天津市宝坻区人民医院肝胆外科,天津市301800

出　　处：《世界华人消化杂志》2020年第16期765-776,共12页World Chinese Journal of Digestology

摘　　要：背景肝细胞癌(hepatocellular carcinoma, HCC)是临床上常见的实体恶性肿瘤,预后较差.本文拟采用生物信息学技术分析PPP1R105基因在肝细胞癌中的表达相关信号通路及其与患者预后关系.同时,采用免疫组织化学法对PPP1R105生物信息数据进行验证.目的探讨PPP1R10基因(Ki-67或MKI67)在HCC中的表达及其临床意义.方法在TCGA数据中,检索PPP1R105基因在各个肿瘤组织中的相对表达情况;分析PPP1R105基因在肝细胞癌组织和癌旁组织中的相对表达水平,并比较是否存在差异.应用蛋白相互作用数据库STRING构建PPP1R105基因编码蛋白相互作用网络.比较PPP1R105高低表达组患者无疾病进展生存(disease free survival, DFS)和总生存(overall survival, OS)是否存在差异.选取我院手术治疗的原发性肝细胞癌患者81例进行回顾性分析,采用免疫组织化学法检测肝细胞癌组织中PPP1R105蛋白表达情况,并与患者的临床特征进行相关性分析.结果PPP1R105基因mRNA在不同肿瘤中表达水平差异并不显著,其表达不具备肿瘤间特异性.在肝细胞癌中,癌组织PPP1R105m RNA表达水平显著高于癌旁正常肝组织(P<0.05),且表达水平与患者临床分期有关(P <0.05).蛋白相互作用网络区域聚集指数为0.99,蛋白相互作用网络富集明显(P<0.01). PPP1R105及其相关基因信号通路主要富集于细胞周期、细胞衰老、病毒致癌及p53信号通路. KIF18B与PPP1R105正相关表达最为显著(rpearson=0.91, P <0.05);而MCELL基因与PPP1R105负相关表达最为显著(rpearson=-0.59, P <0.05);PPP1R105高表达组OS (HR=1.90, P <0.01)和DFS(HR=1.90, P <0.01)显著低于低表达组.PPP1R105蛋白主要表达于细胞核质及核仁, 81例患者中高表达者30例(37.0%).PPP1R105蛋白高表达患者肿瘤大于5cm及TNM分期Ⅲa期患者比例显著高于MIK67蛋白低表达者(P<0.05).结论肝细胞癌患者PPP1R105高表达,其与患者总生存和无疾病进展生存较短有关,可作为肝�BACKGROUND Hepatocellular carcinoma(HCC) is a common malignant tumor with a poor prognosis.In this study,we evaluated the expression of the PPP1R105 gene in HCC and its relationship with prognosis through bioinformatics analysis.Then,we used immunohistochemistry to verify the expression of PPP1R105 protein.AIM To investigate the expression of PPP1R105(Ki-67 or MKI67) in HCC and its clinical significance.METHODS The relative expression data of the PPP1R105 gene in various tumor tissues were retrieved from the tumor protein database and TCGA database and compared between cancer and paired normal tissues.The proteinprotein interaction network(PPI) of PPP1R105 was constructed by using the STRING database.The progression free survival(DFS) and overall survival(OS) between the high and low PPP1R105 expression groups were compared.Eighty-one HCC patients who underwent surgery were retrospectively included in the study,and PPP1R105 protein expression was detected by immunohistochemistry.The relationship between PPP1 R105 protein expression and patients’ features was evaluated.RESULTS The expression levels of PPP1R105 mRNA in different tumors were not significantly different.In HCC,the expression level of PPP1R105 mRNA was significantly higher than that of normal liver tissue,and the expression level was related with clinical stage.The aggregation index of PPI was 0.99,and the enrichment of protein interaction network was significant(P <0.01).PPP1R105 was mainly enriched in cell cycle,cell aging,virus carcinogenesis,and p53 signaling pathway.The positive correlation between KIF18 B and PPP1R105 was the most significant(rperson=0.91,P <0.05),while the negative correlation between MCELL and PPP1R105 was the most significant(rperson=-0.59,P <0.05).DFS(HR=1.90,P <0.01) and OS(HR=1.90,P <0.01) in the high PPP1R105 expression group were significantly shorter than those in the low expression group.PPP1R105 protein was mainly expressed in the cytoplasm and nucleolus of the cells.Of the included 81 patients,30(37.0%) showed high

关 键 词：肝细胞癌 总生存 无疾病进展生存 生物信息分析 免疫组化 

分 类 号：R735.7[医药卫生—肿瘤]