Prediction of Recurrence and Survival in Hepatocellular Carcinoma Based on Two Cox Models Mainly Determined by FoxP3+ Regulatory T Cells
Prediction of Recurrence and Survival in Hepatocellular Carcinoma Based on Two Cox Models Mainly Determined by FoxP3+ Regulatory T Cells
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DOI：
10.1158/1940-6207.capr-12-0379
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发表时间：
2013-06-01
影响因子：
3.3
通讯作者：
Zheng, Shu-Sen
中科院分区：
文献类型：
--
作者：
Lin, Sheng-Zhang;Chen, Kang-Jie;Zheng, Shu-Sen
肝细胞癌（HCC）是一种侵袭性疾病，预后差，预测患者生存的方法有限。已知浸润肿瘤的免疫细胞会影响临床结果。在这里，我们通过免疫组化分析研究了来自两个独立队列的245例标本中肿瘤微环境内免疫浸润的预后意义。使用训练队列构建考克斯回归模型，并在独立队列中进行验证。用受试者工作特征曲线评价诊断准确性。采用流式细胞术、定量PCR和趋化性试验分析肿瘤内调节性T细胞（Treg）的活化、功能和趋化性。我们发现肿瘤中FoxP 3（+）细胞的比例与患者预后呈负相关，而白细胞介素（IL）-17（+）细胞的比例和胰蛋白酶（+）细胞的数量是阳性预测因子。两个考克斯模型在多变量分析中由独立预测因素组成，对肝癌患者预后的诊断准确率较高。FoxP 3（+）细胞的比例显示出最显著的预测能力，在两个模型中具有最高的考克斯评分。此外，我们发现来自FoxP 3（+）比例高的肿瘤的TcR比来自FoxP 3（+）比例低的肿瘤的TcR更有活性和更强大。总之，建立的两个考克斯模型分别对预测肝癌患者的肿瘤复发和生存具有相当的临床价值。在这两种模型中，T细胞在CD 4（+）T细胞中的比例起着核心作用。(C)2013年AACR。
Hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis and limited methods to predict patient survival. Immune cells infiltrating tumors is known to impact clinical outcome. Here, we investigated the prognostic significance of immune infiltration within the tumor microenvironment in 245 specimens from two independent cohorts by immunohistochemical analyses. A Cox regression model was constructed using a training cohort and validated in an independent cohort. The diagnostic accuracy was evaluated by receiver operating characteristic curve. The activation, function, and chemotaxis of intratumoral regulatory T cells (Treg) were analyzed using flow cytometry, quantitative PCR, and chemotaxis assay. We identified that the proportion of FoxP3(+) cells within tumors is negatively associated with patient prognosis, whereas the proportion of interleukin (IL)-17(+) cell and the number of trypase(+) cells are positive predictor. The two Cox models, composed of independent predictors in multivariate analysis, provided a high diagnostic accuracy of prognosis for patients with HCC. The proportion of FoxP3(+) cells showed the most significant predictive power, with the highest Cox score in the two models. Furthermore, we found Tregs from tumor with high FoxP3(+) proportion were more active and powerful than the counterparts from tumor with low FoxP3(+) proportion. In conclusion, two Cox models are established that have considerable clinical value in predicting tumor recurrence and survival of patients with HCC, respectively. In the both models, the proportion of Tregs among CD4(+) T cells plays a central role. (C) 2013 AACR.