Guo Xufeng, Tian Shan, Cao Pan, Xie Yishan, Dong Weiguo
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
J Hepatocell Carcinoma. 2021 Apr 6;8:211-222. doi: 10.2147/JHC.S297601. eCollection 2021.
The effects of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC), in the progression of liver cancer are unknown. In this study, we attempted to clarify the clinical significance and mechanism of PIGC in hepatocellular carcinoma (HCC).
To explore the expression profiles, DNA methylation, mutation status, clinical relevance, and prognostic value of PIGC in patients with HCC, a series of bioinformatic databases and websites were searched. Moreover, numerous vitro experiments were performed to investigate the mechanism of PIGC in the regulation of cancerous liver cells.
Expression of PIGC mRNA and protein was upregulated in cancerous liver specimens compared with normal liver tissues. High expression of PIGC mRNA was related to higher tumor grade, lymphatic metastasis, advanced TNM stage, and TP53 mutation. High expression of PIGC mRNA predicted more unfavorable overall survival (OS) (HR=1.7, P=0.0028) and disease-free survival (DFS) (HR=1.5, P=0.0067) in patients with liver cancer. The mutation rate of PIGC was 10%, and amplification was the most common mutant type. Expression of mRNA was negatively regulated by its DNA methylation (r=-0.398, P<0.0001). Moreover, silencing of in HepG2 cell line inhibited the proliferation and migration and led to cell cycle arrest at G0/G1 stage by reducing cyclinD1, CDK2, CDK4, and CDK6 expression, while overexpression of PIGC in Hcclm3 cell line revealed the opposite effect.
is related to aggressive clinical features, and overexpression of signifies worse survival in patients with HCC. promotes proliferation and migration of cancerous liver cells through the regulation of the cell cycle.
磷脂酰肌醇聚糖锚定生物合成C类（PIGC）在肝癌进展中的作用尚不清楚。在本研究中，我们试图阐明PIGC在肝细胞癌（HCC）中的临床意义及机制。
为探究PIGC在HCC患者中的表达谱、DNA甲基化、突变状态、临床相关性及预后价值，检索了一系列生物信息学数据库和网站。此外，进行了大量体外实验以研究PIGC调控肝癌细胞的机制。
与正常肝组织相比，肝癌组织中PIGC mRNA和蛋白表达上调。PIGC mRNA高表达与更高的肿瘤分级、淋巴转移、晚期TNM分期及TP53突变相关。PIGC mRNA高表达预示肝癌患者总生存期（OS）更差（HR=1.7，P=0.0028）和无病生存期（DFS）更差（HR=1.5，P=0.0067）。PIGC的突变率为10%，扩增是最常见的突变类型。其mRNA表达受DNA甲基化负调控（r=-0.398，P<0.0001）。此外，在HepG2细胞系中沉默PIGC可抑制增殖和迁移，并通过降低细胞周期蛋白D1、细胞周期蛋白依赖性激酶2（CDK2）、细胞周期蛋白依赖性激酶4（CDK4）和细胞周期蛋白依赖性激酶6（CDK6）的表达导致细胞周期停滞在G0/G1期，而在Hcclm3细胞系中过表达PIGC则显示出相反的效果。
PIGC与侵袭性临床特征相关，PIGC过表达表明HCC患者生存更差。PIGC通过调控细胞周期促进肝癌细胞的增殖和迁移。
