Pancreas
Gastroenterology. 2022;163(5):1407–22
Independent validation and assay standardization of improved metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis
Background and aims: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. The authors previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. They therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature.
Methods: The authors evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; non-pancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and a minimalistic metabolic (m-Metabolic) signature and compared them for performance.
Results: The i-Metabolic signature (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve of 97.2% (95% confidence interval [CI]: 97.1–97.3%), 93.5% (95% CI: 93.4–93.7%), and 92.2% (95% CI: 92.1–92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA–IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-9 > 2 U/ml, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-9 < 37 U/ml, 39.7%, 94.1%, and 76.3%, respectively.
Conclusions: The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for pancreatic ductal adenocarcinoma at the time of clinical presentation, warranting further large-scale evaluation.