A prospective multi-cohort study identifies and validates a 5-gene peripheral blood signature predictive of immunotherapy response in non-small cell lung cancer

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-11-06 DOI:10.1186/s12943-024-02160-2

Shaoqiu Chen, Fangfang Liu, Yuanyuan Fu, Chris K. Deng, Jeffrey A. Borgia, Abdul-Ghani Ayman, Masaki Nasu, Mayumi Jijiwa, Hua Yang, Ting Gong, Junlong Wang, Zhougui Ling, Xiaoyan Wang, Hongwei Wang, Qian Chu, Youping Deng

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Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for non-small cell lung cancer (NSCLC). The variability in patient responses necessitates a blood-based, multi-cohort gene signature to predict ICI response in NSCLC. We performed transcriptomic profiling of peripheral blood mononuclear cell (PBMC) and buffy coat (BC) samples from three independent cohorts of NSCLC patients treated with ICIs: a retrospective cohort (PMBCR, n = 59), a retrospective validation cohort (BC, n = 44), and a prospective validation cohort (PBMCP, n = 42). We identified a 5-gene signature (UQCRB, NDUFA3, CDKN2D, FMNL1-DT, and APOL3) predictive of ICI response and validated its clinical utility in the prospective PBMCP cohort. Response was evaluated using RECIST criteria, and patients were followed up for progression-free survival (PFS) and overall survival (OS). In the prospective PBMCP cohort, the 5-gene signature demonstrated high accuracy in stratifying patients into responders and non-responders (AUC = 0.89, 95% CI: 0.80–0.99). Predicted responders exhibited significantly longer PFS compared to predicted non-responders (median: 13.8 months vs. 4.2 months, HR = 0.21, 95% CI: 0.07–0.58, p = 0.005). Our study confirms a 5-gene signature as a key biomarker for ICI response in NSCLC, enhancing treatment precision.

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一项前瞻性多队列研究确定并验证了可预测非小细胞肺癌免疫疗法反应的 5 基因外周血特征

免疫检查点抑制剂（ICIs）彻底改变了非小细胞肺癌（NSCLC）的治疗格局。由于患者反应的差异性，需要一种基于血液的多队列基因特征来预测 NSCLC 的 ICI 反应。我们对接受 ICIs 治疗的三个独立 NSCLC 患者队列的外周血单核细胞（PBMC）和水衣（BC）样本进行了转录组分析：回顾性队列（PMBCR，n = 59）、回顾性验证队列（BC，n = 44）和前瞻性验证队列（PBMCP，n = 42）。我们确定了可预测 ICI 反应的 5 个基因特征（UQCRB、NDUFA3、CDKN2D、FMNL1-DT 和 APOL3），并在前瞻性 PBMCP 队列中验证了其临床实用性。采用 RECIST 标准对反应进行评估，并对患者的无进展生存期（PFS）和总生存期（OS）进行随访。在前瞻性 PBMCP 队列中，5 基因特征在将患者分层为应答者和非应答者方面表现出很高的准确性（AUC = 0.89，95% CI：0.80-0.99）。预测应答者的 PFS 明显长于预测非应答者（中位：13.8 个月 vs. 4.2 个月，HR = 0.21，95% CI：0.07-0.58，p = 0.005）。我们的研究证实了5基因特征是NSCLC ICI反应的关键生物标志物，从而提高了治疗的精确性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.