Fahrmann JF, et al. - In order to detect early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC, researchers applied a training and testing approach to develop and validate a plasma metabolite panel. Substantially improved performance in the detection of early-stage PDAC was exhibited by a metabolite panel in combination with CA19-9, TIMP1, and LRG1 vs a protein panel alone.

Methods

• Experts initially applied a comprehensive metabolomics platform to plasmas collected from 20 PDAC cases and 80 controls.
• They filtered the candidate markers based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts.
• They performed blinded validation of the resulting metabolite panel in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls.
• They evaluated the additive value of combining the metabolite panel with a previously validated protein panel.

Results

• Based on filtering criteria, five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel.
• As per data, for distinguishing between PDAC and healthy controls using the Training Set a combination rule was developed.
• Results demonstrated that in the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] = 0.828 to 0.956).
• By combining the metabolite panel with a previously validated protein marker panel consisting of CA 19–9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P=.02), the performance was further statistically significantly improved.