Natural killer cell and stroma abundance are independently prognostic and predict gastric cancer chemotherapy benefit
Natural killer cell and stroma abundance are independently prognostic and predict gastric cancer chemotherapy benefit
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DOI：
10.1172/jci.insight.136570
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发表时间：
2020-05-07
期刊：
影响因子：
8
通讯作者：
Li, Ruijiang
中科院分区：
文献类型：
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作者：
Li, Bailiang;Jiang, Yuming;Li, Ruijiang
背景。肿瘤微环境（TME）的特定特征可能提供有用的预后信息。我们对胃癌TME的细胞组成和预后前景进行了系统的研究。我们评估了TME内主要基质细胞和免疫细胞的预后意义。我们提出了一种基于tme的综合风险评分，并在6个独立队列中对1678名具有基因表达或免疫组化测量的患者进行了测试。此外，我们设计了一个基于TME特征的患者分类系统。我们确定NK细胞、成纤维细胞和内皮细胞是最可靠的预后标志物。结合这些细胞类型的TME风险评分在调整临床病理变量后是一个独立的预后因素（基因表达，HR [95% CI], 1.42 [1.22-1.66]； IHC,1.34 [1.24-1.45], P < 0.0001）。较高的TME风险评分与各病理阶段的较差生存率（HR范围为2.18-3.11,ID < 0.02）以及仅接受手术的患者一致相关。TME风险评分在分期后提供了额外的预后价值，两者联合使用可提高预测准确性(似然比检验chi(2) = 235.4 vs. 187.6, P < 0.0001；净重分类指数，23%)。TME风险评分可以预测非转移性患者（I-III期）辅助化疗的生存获益（相互作用检验，P < 0.02）。患者分为4种TME亚型，表现出不同的遗传和分子模式，并补充了已建立的基因组和分子亚型。我们开发并验证了基于tme的风险评分作为独立的预后和预测因素，这有可能指导胃癌的个性化治疗。
BACKGROUND. Specific features of the tumor microenvironment (TME) may provide useful prognostic information. We conducted a systematic investigation of the cellular composition and prognostic landscape of the TME in gastric cancer.METHODS. We evaluated the prognostic significance of major stromal and immune cells within the TME. We proposed a composite TME-based risk score and tested it in 6 independent cohorts of 1678 patients with gene expression or IHC measurements. Further, we devised a patient classification system based on TME characteristics.RESULTS. We identified NK cells, fibroblasts, and endothelial cells as the most robust prognostic markers. The TME risk score combining these cell types was an independent prognostic factor when adjusted for clinicopathologic variables (gene expression, HR [95% CI], 1.42 [1.22-1.66]; IHC,1.34 [1.24-1.45], P < 0.0001). Higher TME risk scores consistently associated with worse survival within every pathologic stage (HR range, 2.18-3.11, ID < 0.02) and among patients who received surgery only. The TME risk score provided additional prognostic value beyond stage, and combination of the two improved prognostication accuracy (likelihood-ratio test chi(2) = 235.4 vs. 187.6, P < 0.0001; net reclassification index, 23%). The TME risk score can predict the survival benefit of adjuvant chemotherapy in nonmetastatic patients (stage I-III) (interaction test, P < 0.02). Patients were divided into 4 TME subtypes that demonstrated distinct genetic and molecular patterns and complemented established genomic and molecular subtypes.CONCLUSION. We developed and validated a TME-based risk score as an independent prognostic and predictive factor, which has the potential to guide personalized management of gastric cancer.