Evaluating for correlations between metabolites in patients receiving immunotherapy for metastatic or recurrent NSCLC: an exploratory study based on two cohorts.

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.