Integrating Metabolomics, Mendelian Randomization, and Machine Learning, a Study Flags Phenylalanine and Its Transporter SLC6A14 as Candidate Diagnostic and Therapeutic Targets in Pancreatic Cancer
Integrating plasma metabolomics, Mendelian randomization, and machine learning, this study identified phenylalanine as causally associated with pancreatic cancer among 55 plasma metabolites (IVW OR = 1.641, 95% CI 1.052–2.562, p = 0.029), derived eight related differentially expressed genes, built a random forest diagnostic model from 113 combinations of 12 algorithms (training AUC 0.994; validation AUCs 0.918, 0.983, 0.923), used SHAP to rank SLC6A14 as the top feature, and combined single-cell sequencing, simulated gene knockout, molecular docking, and molecular dynamics to suggest genistein binds SLC6A14 stably, with RT-qPCR confirming high expression of the five model genes in a BxPC-3 versus HPDE6-C7 cell pair.