The prognostic value of peritumoral regulatory T cells and its correlation with intratumoral cyclooxygenase-2 expression in clear cell renal cell carcinoma
The prognostic value of peritumoral regulatory T cells and its correlation with intratumoral cyclooxygenase-2 expression in clear cell renal cell carcinoma
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DOI：
10.1111/j.1464-410x.2008.08151.x
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发表时间：
2009-02-01
影响因子：
4.5
通讯作者：
Xu, Ming
中科院分区：
文献类型：
--
作者：
Li, Jin F.;Chu, Yi W.;Xu, Ming
探讨调节性T细胞（Tregs）在透明细胞肾细胞癌（RCC）中的预后价值及其与环氧化酶-2 （COX-2）表达的相关性。采用免疫组化技术对125例RCC患者的组织微阵列中CD4+、Foxp3+肿瘤浸润淋巴细胞和肿瘤COX-2的表达进行检测。以中位数为阈值，采用Cox回归和Kaplan-Meier分析评估低表达和高表达对预后的影响。比较Tregs和COX-2的表达与临床病理指标的关系。此外，还分析了Tregs及其与COX-2表达的相关性。肿瘤周围Tregs与肿瘤内COX-2表达呈正相关（Spearman秩相关系数0.336,P < 0.001）。瘤周Tregs与TNM分期（P = 0.001）和肿瘤大小（P = 0.002）相关，而瘤内COX-2表达与TNM分期（P = 0.018）和分级（P = 0.013）相关。通过多因素分析，肿瘤周围Tregs升高、TNM分期（III + IV）升高、肿瘤大小（>= 7 cm）增大和核分级（III + IV）升高是总生存期和无病生存期显著缩短的独立预测因素。在透明细胞RCC中，瘤周Tregs增加与预后不良相关。肿瘤内COX-2的高表达可能是Tregs异常聚集的根本原因。这些结果表明，COX-2抑制剂的临床应用可能通过减少RCC中Tregs的转化而使那些肿瘤内COX-2免疫染色较高的患者受益。
To investigate the prognostic value of regulatory T cells (Tregs) and its correlation with cyclooxygenase-2 (COX-2) expression in clear cell renal cell carcinoma (RCC).CD4+, Foxp3+ tumour-infiltrating lymphocytes and tumour COX-2 expression were assessed by immunohistochemistry in tissue microarrays containing RCC from 125 patients. Prognostic effects of low and high expression were evaluated by Cox regression and Kaplan-Meier analysis using the median values as thresholds. The expression of Tregs and COX-2 were compared with the clinicopathological variables. In addition, Tregs and its correlation with COX-2 expression was also analysed.Peritumoral Tregs were positively correlated with intratumoral COX-2 expression (Spearman rank correlation 0.336, P < 0.001). Peritumoral Tregs were associated with TNM stage (P = 0.001) and tumour size (P = 0.002), while intratumoral COX-2 expression was associated with TNM stage (P = 0.018) and grade (P = 0.013). Using multivariate analysis, increased peritumoral Tregs, higher TNM stage (III + IV), larger tumour size (>= 7 cm) and higher nuclear grade (III + IV) were independent predictors for significantly shorter overall survival and disease-free survival.Increased peritumoral Tregs are associated with worse prognosis in clear cell RCC. The high intratumoral COX-2 expression may be the underlying reason for the aberrant gathering of Tregs. These results suggest that clinical application of COX-2 inhibitors may benefit those patients with higher intratumoral COX-2 immunostaining by reducing the transformation of Tregs in RCC.