High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma.
High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma.
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DOI：
10.1186/1479-5876-9-5
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发表时间：
2011-01-05
影响因子：
7.4
通讯作者：
Cai MY
中科院分区：
文献类型：
--
作者：
Li M;Luo RZ;Chen JW;Cao Y;Lu JB;He JH;Wu QL;Cai MY
研究表明，p300参与了广泛的细胞生物学过程的调节，并且已经在某些类型的人类癌症中鉴定了p300的突变。然而，p300在肝细胞癌（HCC）中的表达动态及其临床/预后意义尚不清楚。本研究应用逆转录-聚合酶链反应（RT-PCR）、免疫印迹和免疫组织化学（IHC）方法检测p300蛋白和mRNA在HCC中的表达。采用受试者工作特征（ROC）曲线、斯皮尔曼等级相关、Kaplan-Meier曲线和考克斯比例风险回归模型进行分析。RT-PCR和Western blotting结果显示，与癌旁肝组织相比，p300 mRNA和蛋白在大多数肝癌组织中的表达明显上调。根据ROC曲线，当超过60%的肿瘤细胞被阳性染色时，定义为p300高表达的临界值。p300在HCC中的高表达率为48.8%（60/123），在癌旁肝组织中的高表达率为6.5%（8/123）。p300高表达与AFP水平高、肿瘤体积大、多发、分化差、分期晚有关（P < 0.05）。在单因素生存分析中，发现p300过表达与患者生存期缩短显著相关（P = 0.001）。在不同亚组的HCC患者中，p300表达也是II期（P = 0.007）和III期（P = 0.011）患者的预后指标。重要的是，p300表达在多变量分析中被评估为独立的预后因素（P = 0.021）。因此，一个新的临床病理预后模型与三个不良预后因素（p300表达，AFP水平和血管浸润）的构建。该模型可以显著分层总生存率的风险（低，中，高）（P < 0.0001）。我们的研究结果提供了一个基础的概念，即p300在HCC中的高表达可能是重要的，在收购的侵略性表型，表明p300过表达，通过免疫组化检查，是一个独立的生物标志物与HCC患者预后不良。联合临床病理预后模型可能成为识别具有不同临床结局的HCC患者的有用工具。
It has been suggested that p300 participates in the regulation of a wide range of cell biological processes and mutation of p300 has been identified in certain types of human cancers. However, the expression dynamics of p300 in hepatocellular carcinoma (HCC) and its clinical/prognostic significance are unclear. In this study, the methods of reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate protein/mRNA expression of p300 in HCCs. Receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. Up-regulated expression of p300 mRNA and protein was observed in the majority of HCCs by RT-PCR and Western blotting, when compared with their adjacent non-malignant liver tissues. According to the ROC curves, the cutoff score for p300 high expression was defined when more than 60% of the tumor cells were positively stained. High expression of p300 was examined in 60/123 (48.8%) of HCCs and in 8/123 (6.5%) of adjacent non-malignant liver tissues. High expression of p300 was correlated with higher AFP level, larger tumor size, multiplicity, poorer differentiation and later stage (P < 0.05). In univariate survival analysis, a significant association between overexpression of p300 and shortened patients' survival was found (P = 0.001). In different subsets of HCC patients, p300 expression was also a prognostic indicator in patients with stage II (P = 0.007) and stage III (P = 0.011). Importantly, p300 expression was evaluated as an independent prognostic factor in multivariate analysis (P = 0.021). Consequently, a new clinicopathologic prognostic model with three poor prognostic factors (p300 expression, AFP level and vascular invasion) was constructed. The model could significantly stratify risk (low, intermediate and high) for overall survival (P < 0.0001). Our findings provide a basis for the concept that high expression of p300 in HCC may be important in the acquisition of an aggressive phenotype, suggesting that p300 overexpression, as examined by IHC, is an independent biomarker for poor prognosis of patients with HCC. The combined clinicopathologic prognostic model may become a useful tool for identifying HCC patients with different clinical outcomes.
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