Abstract
INTRODUCTION: Metabolomics has emerged as a powerful method to provide insight into cancer progression, including separating patients into low- and high-risk groups for overall (OS) and progression-free survival (PFS). However, survival prediction based mainly on metabolites obtained from biofluids remains elusive. OBJECTIVES: This proof-of-concept study evaluates metabolites as biomarkers obtained directly from tumor core biopsies along with covariates age, sex, pathological stage at diagnosis (I/II vs. III/VI), histological subtype, and treatment vs. no treatment to risk stratify lung cancer patients in terms of OS and PFS. METHODS: Tumor core biopsy samples obtained during routine lung cancer patient care at the University of Louisville Hospital and Norton Hospital were evaluated with high-resolution 2DLC-MS/MS, and the data were analyzed by Kaplan-Meier survival analysis and Cox proportional hazards regression. A linear equation was developed to stratify patients into low and high risk groups based on log-transformed intensities of key metabolites. Sparse partial least squares discriminant analysis (SPLS-DA) was performed to predict OS and PFS events. RESULTS: Univariable Cox proportional hazards regression model coefficients divided by the standard errors were used as weight coefficients multiplied by log-transformed metabolite intensity, then summed to generate a risk score for each patient. Risk scores based on 10 metabolites for OS and 5 metabolites for PFS were significant predictors of survival. Risk scores were validated with SPLS-DA classification model (AUROC 0.868 for OS and AUROC 0.755 for PFS, when combined with covariates). CONCLUSION: Metabolomic analysis of lung tumor core biopsies has the potential to differentiate patients into low- and high-risk groups based on OS and PFS events and probability.