Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine

Abstract

Background: Better pancreatic cyst fluid biomarkers are needed.

Objective: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers.

Design: Retrospective study.

Setting: Tertiary-care referral center.

Patients: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts.

Intervention: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed.

Main outcome measurements: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve).

Results: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts.

Limitations: Small sample sizes.

Conclusion: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

Keywords: CEA; CI; IPMN; IQR; LC/MS; MCN; MS; ROC; SCA; carcinoembryonic antigen; confidence interval; interquartile range; intraductal papillary mucinous neoplasm; liquid chromatography with mass spectrometry; mass spectrometry; mucinous cystic neoplasm; receiver operating characteristic; serous cystadenoma.