ICIs have demonstrated stunning clinical efficacy in NSCLC. However, most patients do not achieve long-term survival. Minimally invasive collected samples are attracting significant interest as new fields of biomarker study, and metabolomics is one of these growing fields. We focused on the added value of the metabolomic profile as a means of distinguishing long-term survival from short-term survival in NSCLC patients treated with ICIs.: We prospectively recruited 97 patients with stage IV NSCLC who were treated with anti-PD-1 inhibitor, including patients treated with monoimmunotherapy as second-line treatment (Cohort 1), and patients treated with combination immunotherapy as first-line treatment (Cohort 2). Each cohort was divided into long-term survival and short-term survival groups. All blood samples were collected before beginning immunotherapy. Metabolomic profiling of serum was performed by UHPLC-Q-TOF MS analysis. A total of 41 unique metabolites in Cohort 1 and 47 in Cohort 2 were screened. In Cohort 1 and 2, In cohort 1, the top 3 enriched KEGG pathways, as determined through significant different metabolic pathway analysis, were primary bile acid biosynthesis, african trypanosomiasis, and choline metabolism in cancer. In Cohort 2, the top 3 enriched KEGG pathways were the TCA cycle, PPAR signaling pathway, and primary bile acid biosynthesis. The primary bile acid synthesis pathway had significant differences in the long-term survival and short-term survival groups in both Cohort 1 and Cohort 2.Our study suggests that peripheral blood metabolomic analysis is critical for identifying metabolic biomarkers and metabolic pathways responsible for the NSCLC patients treated with ICIs.

中文翻译：

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评估接受转移性或复发性 NSCLC 免疫治疗的患者代谢物之间的相关性：基于两个队列的探索性研究

ICI 在非小细胞肺癌 (NSCLC) 中表现出惊人的临床疗效。然而，大多数患者无法实现长期生存。微创采集样本作为生物标志物研究的新领域引起了人们的极大兴趣，而代谢组学就是这些不断发展的领域之一。我们重点关注代谢组学特征的附加值，作为区分接受 ICI 治疗的 NSCLC 患者的长期生存与短期生存的手段。：我们前瞻性招募了 97 名接受抗 PD-1 治疗的 IV 期 NSCLC 患者抑制剂，包括接受单一免疫疗法作为二线治疗的患者（队列1），以及接受联合免疫疗法作为一线治疗的患者（队列2）。每个队列被分为长期生存组和短期生存组。在开始免疫治疗之前收集所有血液样本。通过 UHPLC-Q-TOF MS 分析进行血清代谢组学分析。筛选了队列 1 中总共 41 种独特的代谢物和队列 2 中的 47 种独特代谢物。在队列 1 和队列 2 中，在队列 1 中，通过显着不同的代谢途径分析确定，前 3 个富集的 KEGG 途径是初级胆汁酸生物合成、非洲锥虫病和癌症中的胆碱代谢。在队列 2 中，前 3 个富集的 KEGG 通路是 TCA 循环、PPAR 信号通路和初级胆汁酸生物合成。在队列 1 和队列 2 中，初级胆汁酸合成途径在长期生存组和短期生存组中均存在显着差异。我们的研究表明，外周血代谢组学分析对于识别导致 NSCLC 的代谢生物标志物和代谢途径至关重要接受 ICI 治疗的患者。