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基于七个免疫特征的口腔鳞状细胞癌根治性切除术后预后评分的建立与验证。

Development and validation of a seven-immune-feature-based prognostic score for oral squamous cell carcinoma after curative resection.

机构信息

Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu, China.

Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.

出版信息

Int J Cancer. 2020 Feb 15;146(4):1152-1163. doi: 10.1002/ijc.32571. Epub 2019 Jul 26.

Abstract

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 × CD3 IM + 1.24 × CD3 CT + 1.701 × CD8 CT + 1.127 × CD45RO IM + 1.348 × CD45RO CT + 1.089 × 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.

摘要

免疫浸润已被越来越多地认为是人类癌症强有力的预后因素。在这里,我们为接受根治性切除术后的口腔鳞状细胞癌 (OSCC) 患者开发并验证了一种基于七种免疫特征的预后评分 (7IFBPS)。通过免疫组织化学结合数字定量,在来自 269 名符合条件的患者的三个独立队列的临床样本中,对七种肿瘤浸润免疫细胞 (TII) 的详细位置和密度进行了 14 种免疫特征的描述。使用 X-tile 软件确定单个免疫特征的最佳截断值。7IFBPS 通过训练队列中的 Kaplan-Meier 和 Cox 回归模型构建,并在测试、验证和联合队列中验证。一致性指数 (C-index)、接受者操作特征和校准曲线用于定义 7IFBPS 在预后预测中的性能。高 CD3 IM(浸润边缘)、CD3 CT(肿瘤中心)、CD8 CT、CD45RO IM、CD45RO CT、FOXP3 IM 和 FOXP3 CT 与改善的生存显著相关。7IFBPS 评分通过以下公式计算:1.041×CD3 IM+1.24×CD3 CT+1.701×CD8 CT+1.127×CD45RO IM+1.348×CD45RO CT+1.089×FOXP3 IM+1.483 FOXP3 CT。高 7IFBPS 在所有队列中均与改善的生存显著相关,是独立的预后预测因子。7IFBPS 预测生存的 C-index 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具有良好的一致性。总的来说,我们的研究结果确立了 7IFBPS 作为一种新的、强大的可切除 OSCC 预后分类器。它有潜力被纳入当前的预后方案,以更好地进行患者分层。

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