Characterizing Plasma-based Metabolomic Signatures for Metastasis in Non-Small Cell Lung Cancer

Abstract: Background/Objectives: The current staging of non-small cell lung cancer (NSCLC) relies on conventional imaging, which lacks sensitivity to detect micrometa-static disease. Functional assessment of NSCLC progression may provide independent information to enhance prediction of metastatic risk.. The objective of this study was to determine if we could identify a metabolomic signature predictive of metastasis in pa-tients with NSCLC treated with definitive radiation. Methods: Plasma samples were collected prospectively from patients enrolled in a clinical trial with non-metastatic NSCLC treated with definitive radiation. Metabolites were extracted and mass spec-trometry-based analysis was performed using a flow injection electrospray (FIE) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) method. Early metastasis was defined as metastasis within 1 year of radiation treatment. Results: The study cohort included 28 patients. FIE-FITCR produced highly reproducible profiles in technical replicates A total of 48 metabolic features were identified to be different in patients with early metastasis compared to patients without early metastasis (all ad-justed p values < 0.05, Welch’s t-test), including glycerophospholipids, sphingolipids, and fatty acyls. In follow up samples collected after initiation of chemotherapy and radiation treatment, a total of 154 metabolic features were significantly altered in patients who developed early metastasis compared to those who did not. Conclusions: We identified several distinct changes in the metabolic profiles of patients with NSCLC who developed metastatic disease within 1 year of definitive radiation. These findings highlight the potential of metabolomic profiling as a predictive tool for assessing met-astatic risk in NSCLC.