Metabolic Characterization of Plasma and Cyst Fluid from Cystic Precursors to Pancreatic Cancer Patients Reveal Metabolic Signatures of Bacterial Infection
Artikel i vetenskaplig tidskrift, 2021

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5 year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insufficient approaches are currently available to determine whether a cyst is going to progress into pancreatic cancer. Recently, we used metabolomics approaches to identify candidate markers of disease progression in patients diagnosed with intraductal papillary mucinous neoplasms (IPMNs) undergoing pancreatic resection. Here, we enrolled an independent cohort to verify the candidate markers from our previous study with orthogonal quantitative methods in plasma and cyst fluid from serous cystic neoplasm and IPMN (either low- or high-grade dysplasia or pancreatic ductal adenocarcinoma). We thus validated these markers with absolute quantitative methods through the auxilium of stable isotope-labeled internal standards in a new independent cohort. Finally, we identified novel markers of IPMN status and disease progression - including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products, and trimethylamine-oxide. We show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. Overall, our findings are interesting per se, owing to the validation of previous markers and identification of novel small molecule signatures of IPMN and disease progression. In addition, our findings further fuel the provoking debate as to whether bacterial infections may represent an etiological contributor to the development and severity of the disease in pancreatic cancer, in like fashion to other cancers (e.g., Helicobacter pylori and gastric cancer).






Ann Morgell

Karolinska Institutet

Julie A. Reisz

University of Colorado Anschutz Medical Campus

Zeeshan Ateeb

Karolinska Institutet

Haleh Davanian

Karolinska Institutet

Susanne Reinsbach

Chalmers, Biologi och bioteknik, Systembiologi

Asif Halimi

Umeå universitet

Karolinska Institutet

Rogier Gaiser

Karolinska Institutet

Roberto Valente

Umeå universitet

Karolinska Institutet

Urban Arnelo

Karolinska Institutet

Umeå universitet

Marco Del Chiaro

University of Colorado Anschutz Medical Campus

Margaret Sällberg Chen

Karolinska Institutet

Angelo D'Alessandro

University of Colorado Anschutz Medical Campus

Journal of Proteome Research

1535-3893 (ISSN) 1535-3907 (eISSN)

Vol. 20 5 2725-2738



Urologi och njurmedicin

Cancer och onkologi





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