Tumor stroma-infiltrating mast cells predict prognosis and adjuvant chemotherapeutic benefits in patients with muscle invasive bladder cancer
Tumor stroma-infiltrating mast cells predict prognosis and adjuvant chemotherapeutic benefits in patients with muscle invasive bladder cancer
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肿瘤基质浸润肥大细胞预测肌层浸润性膀胱癌患者的预后和辅助化疗效果
DOI：
10.1080/2162402x.2018.1474317
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发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Xu, Jiejie
中科院分区：
文献类型：
--
作者：
Liu, Zheng;Zhu, Yu;Xu, Jiejie
摘要肌层浸润性膀胱癌（MIBC）患者哪种亚组可以从辅助化疗（ACT）中获益最多尚不清楚。在这里，我们试图分层MIBC患者与肿瘤浸润肥大细胞（TIM），探讨TIM的预后和预测价值，并提供可能的细胞解释。我们从2002年至2014年期间的两个独立临床中心选择了259名接受根治性膀胱癌的MIBC患者。评估TIM并评估预后和预测价值。采用CIBERSORT方法、基因集富集分析（GSEA）和差异基因表达分析等方法探讨其可能的细胞机制。MIBC标本间质区和上皮区TIMs浸润明显。间质TIM较高的患者总生存期和无复发生存期显著较差（HR = 2.228，95%CI：1.467-3.550; P = 0.001和HR = 1.984，95%CI：1.105-3.374; P = 0.016）。更重要的是，pT 2患者间质TIM低，ACT后死亡和复发的风险较低（HR = 0.233，95%CI：0.020-0.814; P = 0.033和HR = 0.180，95%CI：0.022-0.722; P = 0.031）。TCGA-BLCA队列中TIMs与CD 8 + T细胞呈负相关。免疫组化结果证实高基质TIMs与CD 8 + T细胞呈负相关（斯皮尔曼rho =-0.215，P < 0.001）。差异基因表达表明，低TIM可能代表MIBC的免疫激活状态。总之，高基质TIM浸润是MIBC患者的独立不利因素。低基质TIM的患者可能从ACT中获益最多，特别是在pT 2期。
ABSTRACT Which subgroups patients with muscle-invasive bladder cancer (MIBC) could benefit most from adjuvant chemotherapy (ACT) is blurred. Here we tried to stratify MIBC patients with tumor infiltrating mast cells (TIMs), explore the prognostic and predictive value of TIMs, and provide possible cellular explanations. We selected 259 MIBC patients who underwent radical cystectomy from two independent clinical centers between 2002 and 2014. TIMs were evaluated and prognostic and predictive value was assessed. The CIBERSORT method, Gene Set Enrichment Analysis (GSEA) and differential gene expression analyses were performed to explore the possible cellular mechanisms. TIMs infiltration was distinct between stromal and epithelial area of MIBC specimens. Patients with higher stromal TIMs had a significant worse overall survival and recurrence free survival (HR = 2.228, 95%CI: 1.467–3.550; P = 0.001 and HR = 1.984, 95%CI: 1.105–3.374; P = 0.016). More importantly, pT2 patients with low stromal TIMs tended to have a lower risk of death and recurrence after ACT (HR = 0.233, 95%CI: 0.020–0.814; P = 0.033 and HR = 0.180, 95%CI: 0.022–0.722; P = 0.031). A negative correlativity between TIMs and CD8 + T cells was identified on TCGA-BLCA cohort. Immunohistochemistry results validated that high stromal TIMs were negatively correlated with CD8 + T cells (Spearman’s rho = -0.215, P < 0.001). Differential gene expression suggested that low TIMs might represent a state of immune activation in MIBC. To conclude, high stromal TIMs infiltration was an independent unfavorable prognosticator for MIBC patients. Patients with low stromal TIMs might benefit the most from ACT, especially in pT2 stage.