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—dglucose 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.

Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts

“…Glucose is commonly measured using spectrophotometric technologies that do not rely on antibody specifi city, and there is no heterogeneity in the glucose molecule as there might be with a tumor marker such as CEA. Th ere has only been one other study regarding the use of glucose to diff erentiate mucinous from non-mucinous cysts ( 9 ). In this study, metabolomic profi ling identifi ed glucose as a candidate molecule with an AUC of 0.88.…”

“…In an earlier study that included an exploratory metabolomic analysis of pancreatic cyst fl uid, glucose appeared to accurately diff erentiate non-mucinous from pre-malignant mucinous cysts with 94% sensitivity and 64% specifi city using a cutoff value of 66 mg/dl (AUC 0.88) ( 9 ). In the following study, we seek to further validate this observation regarding glucose using point-ofcare instruments in a larger cohort and compare its performance to CEA.…”

“…Nineteen of these cysts were also used in the exploratory metabolomics study ( 9 ). Of the 65 tested for glucose, 39 also had CEA measured.…”

Cyst Fluid Biomarkers - Diagnosis and Prediction of Malignancy for Cystic Lesions of the Pancreas

“…However, studies have shown that cyst fluid amylase levels are similar in IPMNs and MCNs, and thus cannot be used to differentiate these two types of cysts [27]. There has been an interest in using cyst fluid glucose levels to differentiate IPMNs and MCNs from other types of cysts [28,29]. A recent study evaluated this in 153 patients all of whom had undergone surgical resection [30].…”

Management of serous cystic neoplasms of the pancreas

“…Based on a preliminary experience, Park and co-workers have found that two metabolites, glucose and kynurenine, were differentially abundant in SCAs [52]. In particular, when cyst glucose levels of SCAs were compared with those of lesions that were not SCAs (pseudocysts, IPMNs, mucinous cystic neoplasms and cancer), the median cyst glucose level was significantly elevated, with an receiver operator characteristic curve of 0.93 (95% CI: 0.86-1.0).…”