Development and validation of a seven-immune-feature-based prognostic score for oral squamous cell carcinoma after curative resection
Development and validation of a seven-immune-feature-based prognostic score for oral squamous cell carcinoma after curative resection
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口腔鳞状细胞癌根治性切除后基于七项免疫特征的预后评分的开发和验证
DOI：
10.1002/ijc.32571
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发表时间：
2019-07-26
影响因子：
6.4
通讯作者：
Cheng, Jie
中科院分区：
文献类型：
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作者：
Zhou, Chen;Diao, Pengfei;Cheng, Jie
免疫浸润已越来越多地被认为是人类癌症的强有力的预后因素。在这里，我们开发并验证了一个七免疫功能为基础的预后评分（7IFBPS）的口腔鳞状细胞癌（OSCC）根治性切除术后的患者。通过免疫组织化学结合数字定量，在三个独立队列的269例符合条件的患者的临床样本中，对7种类型的肿瘤浸润免疫细胞（TII）的详细位置和密度进行了14项免疫特征的表征。使用X-tile软件产生个体免疫特征的最佳截止值。在训练队列中采用Kaplan-Meier和考克斯回归模型构建7个IFBPS，并在测试、验证和合并队列中进行验证。采用一致性指数（C指数）、受试者工作特征和校准曲线来确定7IFBPS在预后预测中的性能。高CD 3 IM（浸润性边缘）、CD 3 CT（肿瘤中心）、CD 8 CT、CD 45 RO IM、CD 45 RO CT、FOXP 3 IM和FOXP 3 CT与生存率改善显著相关。使用以下公式计算7IFBPS评分：1.041 x CD 3 IM + 1.24 x CD 3 CT + 1.701 x CD 8 CT + 1.127 x CD 45 RO IM + 1.348 x CD 45 RO CT + 1.089 x FOXP 3 IM + 1.483 FOXP 3 CT。在所有队列中，高7IFBPS与生存率改善显著相关，并可作为独立的预后预测因子。7IFBPS预测生存的C指数为0.668（95%CI，0.609-0.726）。生存概率的校准曲线显示7IFBPS预测与实际观察之间的良好协议。总的来说，我们的研究结果建立了7IFBPS作为一种新的功能强大的可切除的口腔鳞癌预后分类。它有可能被纳入目前的预后制度，以更好地患者分层。
Immune infiltrates have been increasingly recognized as robust prognostic factors for human cancer. Here, we developed and validated a seven-immune-feature-based prognostic score (7IFBPS) for patients with oral squamous cell carcinoma (OSCC) after curative resection. Fourteen immune features regarding detailed locations and densities of seven types of tumor-infiltrating immune cells (TIIs) were characterized in clinical samples from 269 eligible patients in three independent cohorts by immunohistochemistry coupled with digital quantitation. Optimal cutoff values for individual immune features were yielded using X-tile software. The 7IFBPS was constructed by Kaplan-Meier and Cox regression model in training cohort and verified in testing, validation and combined cohorts. Concordance index (C-index), receiver operating characteristics and calibration curves were employed to define the performance of 7IFBPS in prognostic prediction. High CD3 IM (invasive margin), CD3 CT (center of tumor), CD8 CT, CD45RO IM, CD45RO CT, FOXP3 IM and FOXP3 CT significantly associated with improved survival. The 7IFBPS score was calculated using the formula: 1.041 x CD3 IM + 1.24 x CD3 CT + 1.701 x CD8 CT + 1.127 x CD45RO IM + 1.348 x CD45RO CT + 1.089 x FOXP3 IM + 1.483 FOXP3 CT. High 7IFBPS significantly associated with improved survival in all cohorts and served as an independent prognostic predictor. The C-index of 7IFBPS for predicting survival was 0.668 (95% CI, 0.609-0.726). Calibration curves for survival probability showed good agreement between prediction by 7IFBPS and actual observation. Collectively, our findings established the 7IFBPS as a novel powerful prognostic classifier for resectable OSCC. It holds potentials to be incorporated into current prognostic regime to better patient stratification.