Zhangyuan Guangyan, Yin Yin, Zhang Wenjie, Yu WeiWei, Jin Kangpeng, Wang Fei, Huang Ruyi, Shen Haiyuan, Wang Xiaochen, Sun Beicheng
Liver Transplantation Center of the First Affiliated Hospital and Department of Hepatobilliary Surgery of Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Cell Physiol Biochem. 2018;46(6):2335-2346. doi: 10.1159/000489625. Epub 2018 May 4.
BACKGROUND/AIMS: During the occurrence and progression of hepatocellular carcinoma (HCC), phosphotyrosine phosphatases (PTPs) are usually described as tumor suppressors or proto-oncogenes, and to some degree are correlated with the prognosis of HCC.
A total of 321 patients from the Cancer Genome Atlas (TCGA) database and 180 patients from our validated cohort with hepatocellular carcinoma were recruited in this study. Kaplan-Meier, univariate and multivariate Cox proportional hazards model were used to evaluate the risk factors for survival. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were applied to detect the expression levels of PTP genes.
After screening the data of TCGA, we identified five PTPs as HCC overall survival related PTP genes, among which only three (PTPN12, PTPRN, PTPN18) exhibited differential expression levels in our 180 paired HCC and adjacent tissues (P< 0.001). Further analysis revealed that expression of PTPN18 was positively, but PTPRN was negatively associated with prognosis of HCC both in TCGA cohort and our own cohort. As to PTPN12, results turned out to be opposite according to HBV status. In detail, higher expression of PTPN12 was associated with better outcome in HBV group but worse prognosis in Non-HBV group.
Our results suggested that PTPN12, PTPRN and PTPN18 were independent prognostic factors in HCC.
背景/目的：在肝细胞癌（HCC）的发生和发展过程中，磷酸酪氨酸磷酸酶（PTPs）通常被描述为肿瘤抑制因子或原癌基因，并且在一定程度上与HCC的预后相关。
本研究招募了来自癌症基因组图谱（TCGA）数据库的321例患者以及我们验证队列中的180例肝细胞癌患者。采用Kaplan-Meier法、单因素和多因素Cox比例风险模型评估生存的危险因素。应用定量实时PCR（qRT-PCR）和免疫组织化学（IHC）检测PTP基因的表达水平。
筛选TCGA数据后，我们鉴定出5个PTPs为与HCC总生存相关的PTP基因，其中只有3个（PTPN12、PTPRN、PTPN18）在我们的180对HCC及癌旁组织中表现出差异表达水平（P<0.001）。进一步分析显示，在TCGA队列和我们自己的队列中，PTPN18的表达与HCC预后呈正相关，而PTPRN与HCC预后呈负相关。至于PTPN12，根据HBV状态结果相反。具体而言，PTPN12表达较高在HBV组与较好的预后相关，但在非HBV组与较差的预后相关。
我们的结果表明，PTPN12、PTPRN和PTPN18是HCC的独立预后因素。
