Metabolomics Profiling of EUS-FNA Sample Predicts Advanced Pancreatic Adenocarcinoma Prognosis

Abstract Background Effective anti-tumor medicine for individual cases with different prognosis risks is urgent for pancreatic adenocarcinoma (PAC) therapy. Metabolic therapy is a promising strategy for PAC. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a suitable technique for the biopsy of pancreatic mass. Here, we first perform metabolome analysis with EUS-FNA samples to identify prognostic biomarkers and potential therapeutic targets in advanced PAC. Methods PAC underwent EUS-FNA between October 2018 to March 2019 were enrolled. The cytological sample was delivered for liquid chromatography coupled with mass spectrometry (LC-MS). Results A total of 60 advanced PAC with median survival of 390 days were enrolled for metabolome analysis, and 402 unique metabolites were identified. In multivariate analysis, a two-metabolite (cholesterol glucuronide and taurocholic acid 3-sulfate) risk score [hazard ratio (HR) = 1.983, 95% confidence interval (CI) = 1.362–2.887, p < 0.001] was constructed and proved to be independent predictors for overall survival. The C-index of the risk score was 0.64 (95% CI: 0.70–0.59). Patients in the high-risk and low-risk groups stratified by the risk score suffered different prognosis (median survival time 194 versus 480 days, p < 0.001). The area under the curve at 1 year was 0.685. The nomogram was depicted by combining the risk score with clinical parameters. The C-index was 0.67 (95% CI: 0.73–0.62). Finally, WGCNA identified three distinct modules and major enriched in glucose-alanine cycle and α-linolenic acid metabolism. Conclusions A two-metabolite risk score and nomogram with the ability to predict survival of PAC were generated. The two metabolites both showed an association with bile acid accumulation. The glucose-alanine cycle and α-linolenic acid metabolism were highly active in advanced PAC, which might be the target in future therapy.