Peng S-L, Yao D-B, Zhao Y, Xu F, Jia C-J, Xu Y-Q, Dai C-L
Department of Hepatobiliary Surgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang, China.
Eur Rev Med Pharmacol Sci. 2015 Jan;19(1):38-44.
The p53 upregulated modulator of apoptosis (PUMA) is a potent apoptosis inducer that is downexpressed in various tumor types. The aim of this study was to explore the prognostic significance of PUMA expression in patients with hepatitis B virus-related hepatocellular carcinoma (HCC).
PUMA expressions were examined in 80 pairs of tissues to compare its expression between cancer tissues and paired noncancerous liver tissues using immunohistochemistry (IHC). Relationship between the PUMA expression level and clinicopathological characteristics and clinic outcomes was analyzed.
PUMA protein was all positive in paired non-tumor tissue samples. PUMA were downregulated in 61.25% (49/80) of tumor tissues compared with non-tumor tissues. PUMA levels in cancer tissues were significantly lower than non-tumor in patients with recurrence-related factors and patients at higher stage (stage II, III) (p < 0.05). In addition, the expressions level in tumor tissues showed a significant correlation with advanced TNM stage (p = 0.013) and present of recurrence-related factors (p = 0.002). Furthermore, Kaplan-Meier survival analysis revealed that weak PUMA expression was associated with poor 3-year disease-free survival (DFS) and overall survival (OS) in HCC patients. Finally, multivariate analyses identified that PUMA was an independent poor-prognostic predictor for DFS and OS in patients with HBV-related HCC.
Our results suggest that PUMA expression is a novel prognostic indicator in HBV-related HCC and may be a potential target for diagnosis and gene therapy.
p53上调凋亡调节因子（PUMA）是一种强效的凋亡诱导剂，在多种肿瘤类型中表达下调。本研究旨在探讨PUMA表达在乙型肝炎病毒相关肝细胞癌（HCC）患者中的预后意义。
采用免疫组织化学（IHC）检测80对组织中PUMA的表达，以比较癌组织与配对的非癌肝组织之间的表达情况。分析PUMA表达水平与临床病理特征及临床结局之间的关系。
配对的非肿瘤组织样本中PUMA蛋白均呈阳性。与非肿瘤组织相比，61.25%（49/80）的肿瘤组织中PUMA表达下调。复发相关因素患者和晚期（II期、III期）患者的癌组织中PUMA水平显著低于非肿瘤组织（p<0.05）。此外，肿瘤组织中的表达水平与晚期TNM分期（p=0.013）和复发相关因素的存在（p=0.002）显著相关。此外，Kaplan-Meier生存分析显示，PUMA弱表达与HCC患者3年无病生存率（DFS）和总生存率（OS）较差相关。最后，多因素分析确定PUMA是HBV相关HCC患者DFS和OS的独立不良预后预测指标。
我们的结果表明，PUMA表达是HBV相关HCC的一种新的预后指标，可能是诊断和基因治疗的潜在靶点。
