196P - Serum metabolomics to determine survival of immunotherapy for advanced non-small cell lung cancer: Metabolomic analysis based on two cohorts

Background

Noninvasively collected samples are attracting significant interest as new areas of biomarker study in immune checkpoint inhibitors (ICIs) field, and metabolomics is one of these growing ones. 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.

Methods

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 two groups, long-term survival and short-term survival. All blood samples were collected before beginning immunotherapy. Metabolomic profiling of serum was performed by UHPLC-Q-TOF MS analysis. Multivariate data analysis, including Pareto-scaled principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA), was performed.

Results

A total of 41 differential metabolites in Cohort 1 and 47 in Cohort 2 were screened. Among them, 8 common metabolites in ESI^- mode and 11 in ESI⁺ mode were significantly associated with both PFS and OS in cohort 1. In cohort 2, 3 metabolites in ESI^- mode and 6 in ESI⁺ mode were significantly associated with both PFS and OS. In cohort 1, the top 3 enriched KEGG pathways, as determined through significant differential 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 citrate cycle (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.

Conclusions

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, and the primary bile acid synthesis pathway may be the important one.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Zhejiang Cancer Hospital.

Funding

the Science and Technology Program for Health and Medicine in Zhejiang Province, China (Grant No. 2021KY541), and the Natural Scientific Foundation of Zhejiang Province, China (Grant No. LY19H160007).

Disclosure

All authors have declared no conflicts of interest.