Clinical Significance and Molecular Annotation for PD-L1 Negative Advanced Non-Small Cell Lung Cancer with Sensitivity to Responsive to Dual PD-1/CTLA-4 Blockade.

IF 6.2 Q1 IMMUNOLOGY ImmunoTargets and Therapy Pub Date : 2024-09-06 eCollection Date: 2024-01-01 DOI:10.2147/ITT.S476040
Li Wang, Li Liu, Jing Zhao, Xin Yu, Chunxia Su
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引用次数: 0

Abstract

Background: Immunotherapy has become the standard treatment for driving gene-negative advanced non-small cell lung cancer (NSCLC). However, compared to PD-L1-positive patients, the efficacy of Anti-PD-(L)1 monotherapy is suboptimal in PD-L1-negative advanced NSCLC. In this study, we aim to analyze the optimal immunotherapy approach for PD-L1-negative NSCLC patients and develop a new nomogram to enhance the clinical predictability of immunotherapy for NSCLC patients.

Methods: In this study, we retrieved clinical information and genomic data from cBioPortal for NSCLC patients undergoing immunotherapy. Cox regression analyses were utilized to screen the clinical information and genomic data that related to survival. The prognostic-relate genes function was studied by comprehensive bioinformatics analyses. The Kaplan-Meier plot method was employed for survival analysis.

Results: A total of 199 PD-L1-negative NSCLC patients were included in this study. Among them, 165 patients received Anti-PD-(L)1 monotherapy, while 34 patients received Anti-PD-(L)1+Anti-CTLA-4 combination therapy. The Anti-PD-(L)1+Anti-CTLA-4 combination therapy demonstrated significantly higher PFS compared to the Anti-PD-(L)1 monotherapy. The mutation status of KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 were found to correlate with PFS. Utilizing the clinicopathological parameters and genomic data of the patients, a novel nomogram was developed to predict the prognosis of Anti-PD-(L)1+Anti-CTLA-4 combination therapy.

Conclusion: Our study revealed that KRAS, ANO1, COL14A1, LTBP1. ERBB4 and PCSK5 mutation could serve as predictive biomarkers for patients with Anti-PD-(L)1+Anti-CTLA-4 combination therapy. Our systematic nomogram demonstrates significant potential in predicting the prognosis for NSCLC patients with responsive to dual PD-1/CTLA-4 blockade.

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PD-L1阴性晚期非小细胞肺癌对PD-1/CTLA-4双重阻断敏感的临床意义和分子注释。
背景:免疫疗法已成为基因阴性晚期非小细胞肺癌(NSCLC)的标准治疗方法。然而,与PD-L1阳性患者相比,抗PD-(L)1单药治疗在PD-L1阴性晚期NSCLC中的疗效并不理想。本研究旨在分析PD-L1阴性NSCLC患者的最佳免疫治疗方法,并开发新的提名图,以提高NSCLC患者免疫治疗的临床可预测性:在这项研究中,我们从cBioPortal检索了接受免疫治疗的NSCLC患者的临床信息和基因组数据。方法:我们从 cBioPortal 上检索了接受免疫治疗的 NSCLC 患者的临床信息和基因组数据,并利用 Cox 回归分析筛选出与生存相关的临床信息和基因组数据。通过综合生物信息学分析研究了预后相关基因的功能。采用Kaplan-Meier图法进行生存分析:本研究共纳入199例PD-L1阴性NSCLC患者。其中,165名患者接受了抗PD-(L)1单药治疗,34名患者接受了抗PD-(L)1+抗CTLA-4联合治疗。与抗PD-(L)1单药治疗相比,抗PD-(L)1+抗CTLA-4联合疗法的PFS明显更高。KRAS、ANO1、COL14A1、LTBP1.ERBB4和PCSK5的突变状态与PFS相关。利用患者的临床病理参数和基因组数据,我们绘制了一个新的提名图来预测抗-PD-(L)1+抗-CTLA-4联合疗法的预后:我们的研究发现,KRAS、ANO1、COL14A1、LTBP1、ERBB4和PCSK5对癌症患者的预后有重要影响。结论:我们的研究表明,KRAS、ANO1、COL14A1、LTBP1、ERBB4 和 PCSK5 突变可作为抗-PD-(L)1+抗-CTLA-4 联合疗法患者的预测性生物标志物。我们的系统提名图在预测对PD-1/CTLA-4双重阻断治疗有反应的NSCLC患者的预后方面具有重大潜力。
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来源期刊
CiteScore
16.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊介绍: Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.
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