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PD-L1 蛋白表达与乳腺癌患者接受新辅助化疗后的良好临床结局相关,且可用于无病生存和总生存的预测。

PD-L1 Protein Expression Is Associated With Good Clinical Outcomes and Nomogram for Prediction of Disease Free Survival and Overall Survival in Breast Cancer Patients Received Neoadjuvant Chemotherapy.

机构信息

Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Front Immunol. 2022 May 20;13:849468. doi: 10.3389/fimmu.2022.849468. eCollection 2022.

Abstract

OBJECTIVE

This study aims to investigate the potential prognostic significance of programmed death ligand-1 (PD-L1) protein expression in tumor cells of breast cancer patients received neoadjuvant chemotherapy (NACT).

METHODS

Using semiquantitative immunohistochemistry, the PD-L1 protein expression in breast cancer tissues was analyzed. The correlations between PD-L1 protein expression and clinicopathologic characteristics were analyzed using Chi-square test or Fisher's exact test. The survival curve was stemmed from Kaplan-Meier assay, and the log-rank test was used to compare survival distributions against individual index levels. Univariate and multivariate Cox proportional hazards regression models were accessed to analyze the associations between PD-L1 protein expression and survival outcomes. A predictive nomogram model was constructed in accordance with the results of multivariate Cox model. Calibration analyses and decision curve analyses (DCA) were performed for the calibration of the nomogram model, and subsequently adopted to assess the accuracy and benefits of the nomogram model.

RESULTS

A total of 104 breast cancer patients received NACT were enrolled into this study. According to semiquantitative scoring for IHC, patients were divided into: low PD-L1 group (61 cases) and high PD-L1 group (43 cases). Patients with high PD-L1 protein expression were associated with longer disease free survival (DFS) (mean: 48.21 months vs. 31.16 months; P=0.011) and overall survival (OS) (mean: 83.18 months vs. 63.31 months; P=0.019) than those with low PD-L1 protein expression. Univariate and multivariate analyses indicated that PD-L1, duration of neoadjuvant therapy, E-Cadherin, targeted therapy were the independent prognostic factors for patients' DFS and OS. Nomogram based on these independent prognostic factors was used to evaluate the DFS and OS time. The calibration plots shown PD-L1 based nomogram predictions were basically consistent with actual observations for assessments of 1-, 3-, and 5-year DFS and OS time. The DCA curves indicated the PD-L1 based nomogram had better predictive clinical applications regarding prognostic assessments of 3- and 5-year DFS and OS, respectively.

CONCLUSION

High PD-L1 protein expression was associated with significantly better prognoses and longer DFS and OS in breast cancer patients. Furthermore, PD-L1 protein expression was found to be a significant prognostic factor for patients who received NACT.

摘要

目的

本研究旨在探讨肿瘤细胞程序性死亡配体-1(PD-L1)蛋白表达在接受新辅助化疗(NACT)的乳腺癌患者中的潜在预后意义。

方法

采用半定量免疫组织化学方法分析乳腺癌组织中 PD-L1 蛋白的表达。采用卡方检验或 Fisher 确切检验分析 PD-L1 蛋白表达与临床病理特征的相关性。生存曲线源自 Kaplan-Meier 分析,对数秩检验用于比较个体指标水平的生存分布。采用单因素和多因素 Cox 比例风险回归模型分析 PD-L1 蛋白表达与生存结局之间的相关性。根据多因素 Cox 模型的结果构建预测列线图模型。对列线图模型进行校准分析和决策曲线分析(DCA),以评估列线图模型的校准,并随后用于评估列线图模型的准确性和获益。

结果

共纳入 104 例接受 NACT 的乳腺癌患者进行本研究。根据免疫组化的半定量评分,患者分为:低 PD-L1 组(61 例)和高 PD-L1 组(43 例)。高 PD-L1 蛋白表达患者的无病生存期(DFS)(平均:48.21 个月比 31.16 个月;P=0.011)和总生存期(OS)(平均:83.18 个月比 63.31 个月;P=0.019)均长于低 PD-L1 蛋白表达患者。单因素和多因素分析表明,PD-L1、新辅助治疗持续时间、E-钙黏蛋白、靶向治疗是患者 DFS 和 OS 的独立预后因素。基于这些独立预后因素的列线图用于评估 DFS 和 OS 时间。校准图显示基于 PD-L1 的列线图预测与实际观察结果基本一致,用于评估 1、3 和 5 年的 DFS 和 OS 时间。DCA 曲线表明,基于 PD-L1 的列线图在评估 3 年和 5 年 DFS 和 OS 的预后方面具有更好的预测临床应用价值。

结论

高 PD-L1 蛋白表达与乳腺癌患者的预后显著改善及更长的 DFS 和 OS 相关。此外,PD-L1 蛋白表达是接受 NACT 的患者的一个重要预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8661/9163312/fdad2674a517/fimmu-13-849468-g001.jpg

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