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PD-L1和肿瘤突变负荷对非小细胞肺癌短期疗效预后的预测价值及预测模型构建

Predictive value of PD-L1 and TMB for short-term efficacy prognosis in non-small cell lung cancer and construction of prediction models.

作者信息

Shi Shuling, Wang Yingyi, Wu Jingjing, Zha Boya, Li Peihong, Liu Yukun, Yang Yuchuan, Kong Jinglin, Gao Shibo, Cui Haiyang, Huangfu Linkuan, Sun Xiaocong, Li Zhikai, Liang Tiansong, Zheng Yingjuan, Yang Daoke

机构信息

Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Institute of Radiotherapy and Critical Care Oncology, Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Front Oncol. 2024 May 2;14:1342262. doi: 10.3389/fonc.2024.1342262. eCollection 2024.

Abstract

OBJECTIVE

To investigate the correlation between programmed death ligand 1(PD-L1), tumor mutation burden (TMB) and the short-term efficacy and clinical characteristics of anti-PD-1 immune checkpoint inhibitor combination chemotherapy in NSCLC patients. The efficacy of the prediction model was evaluated.

METHODS

A total of 220 NSCLC patients receiving first-line treatment with anti-PD-1 immune checkpoint inhibitor combined with chemotherapy were retrospectively collected. The primary endpoint was short-term efficacy ORR. The correlation between short-term efficacy, PD-L1, TMB, and clinical characteristics using χ2 test or t-test was evaluated. Screen the independent prognostic factors using univariate and multivariate logistic regression analyses, and construct a nomogram prediction model using the "rms" package in R software. Using receiver operating characteristic (ROC) curve analysis to evaluate the independent Prognostic factors and the prediction model. Using decision curve analysis (DCA) to verify the superiority of the prediction model.

RESULTS

The mean values of PD-L1, TMB, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, and albumin were the highest in the ORR group, PD-L1 expression and TMB correlated with epidermal growth factor receptor expression. Multivariate analyses showed that PD-L1, TMB, and neutrophil were independent prognostic factors for ORR. The area under the ROC curve (AUC) values of the ROC constructed based on these three indicators were 0.7104, 0.7139, and 0.7131, respectively. The AUC value under the ROC of the nomogram model was 0.813. The DCA of the model showed that all three indicators used together to build the prediction model of the net return were higher than those of the single indicator prediction model.

CONCLUSION

PD-L1, TMB, and neutrophils are independent prognostic factors for short-term efficacy. The nomogram prediction model constructed using these three indicators can further improve predictive efficacy of ICIs in patients with NSCLC.

摘要

目的

探讨程序性死亡配体1(PD-L1)、肿瘤突变负荷(TMB)与非小细胞肺癌(NSCLC)患者抗PD-1免疫检查点抑制剂联合化疗的短期疗效及临床特征之间的相关性。评估预测模型的疗效。

方法

回顾性收集220例接受一线抗PD-1免疫检查点抑制剂联合化疗的NSCLC患者。主要终点为短期疗效客观缓解率(ORR)。采用χ2检验或t检验评估短期疗效、PD-L1、TMB与临床特征之间的相关性。通过单因素和多因素逻辑回归分析筛选独立预后因素,并使用R软件中的“rms”包构建列线图预测模型。采用受试者工作特征(ROC)曲线分析评估独立预后因素和预测模型。使用决策曲线分析(DCA)验证预测模型的优越性。

结果

ORR组中PD-L1、TMB、中性粒细胞、淋巴细胞、中性粒细胞与淋巴细胞比值及白蛋白的均值最高,PD-L1表达和TMB与表皮生长因子受体表达相关。多因素分析显示,PD-L1、TMB和中性粒细胞是ORR的独立预后因素。基于这三个指标构建的ROC曲线下面积(AUC)值分别为0.7104、0.7139和0.7131。列线图模型的ROC下AUC值为0.813。模型的DCA显示,三者共同构建的预测模型的净收益高于单一指标预测模型。

结论

PD-L1、TMB和中性粒细胞是短期疗效的独立预后因素。使用这三个指标构建的列线图预测模型可进一步提高ICIs对NSCLC患者的预测疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/11096522/31f9a99bf3dd/fonc-14-1342262-g001.jpg

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