Independent validation and assay standardization of improved metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis
Background & Aims - Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 October 2022
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| In: |
Gastroenterology
Year: 2022, Volume: 163, Issue: 5, Pages: 1407-1422 |
| ISSN: | 1528-0012 |
| DOI: | 10.1053/j.gastro.2022.07.047 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1053/j.gastro.2022.07.047 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S001650852200823X 
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| Author Notes: | Ujjwal M. Mahajan, Bettina Oehrle, Simon Sirtl, Ahmed Alnatsha, Elisabetta Goni, Ivonne Regel, Georg Beyer, Marlies Vornhülz, Jakob Vielhauer, Ansgar Chromik, Markus Bahra, Fritz Klein, Waldemar Uhl, Tim Fahlbusch, Marius Distler, Jürgen Weitz, Robert Grützmann, Christian Pilarsky, Frank Ulrich Weiss, M. Gordian Adam, John P. Neoptolemos, Holger Kalthoff, Roland Rad, Nicole Christiansen, Bianca Bethan, Beate Kamlage, Markus M. Lerch and Julia Mayerle |
| Summary: | Background & Aims - Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We 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. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature. - Methods - We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic 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 minimalistic metabolic (m-Metabolic) signatures, and compared them for performance. - Results - The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (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 PDAC at the time of clinical presentation, warranting further large-scale evaluation. |
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| Item Description: | Online verfügbar 21 Juli 2022, Artikelversion 20 Oktober 2022 Gesehen am 23.03.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0012 |
| DOI: | 10.1053/j.gastro.2022.07.047 |