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Metabolic Character...
Metabolic Characterization of Plasma and Cyst Fluid from Cystic Precursors to Pancreatic Cancer Patients Reveal Metabolic Signatures of Bacterial Infection
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- Morgell, Ann (author)
- Karolinska Institutet
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Reisz, Julie A. (author)
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- Ateeb, Zeeshan (author)
- Karolinska Institutet
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- Davanian, Haleh (author)
- Karolinska Institutet
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- Reinsbach, Susanne, 1983 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Halimi, Asif (author)
- Umeå universitet,Kirurgi,Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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- Gaiser, Rogier (author)
- Karolinska Institutet
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- Valente, Roberto (author)
- Umeå universitet,Kirurgi,Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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- Arnelo, Urban (author)
- Umeå universitet,Karolinska Institutet,Kirurgi,Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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Del Chiaro, Marco (author)
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- Chen, Margaret Sällberg (author)
- Karolinska Institutet
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D'Alessandro, Angelo (author)
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(creator_code:org_t)
- 2021-03-15
- 2021
- English.
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 20:5, s. 2725-2738
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Abstract
Subject headings
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- 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).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Keyword
- microbiome
- IPMN
- metabolomics
- cyst
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Morgell, Ann
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Reisz, Julie A.
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Ateeb, Zeeshan
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Davanian, Haleh
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Reinsbach, Susan ...
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Halimi, Asif
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show more...
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Gaiser, Rogier
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Valente, Roberto
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Arnelo, Urban
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Del Chiaro, Marc ...
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Chen, Margaret S ...
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D'Alessandro, An ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Urology and Neph ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Surgery
- Articles in the publication
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Journal of Prote ...
- By the university
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Chalmers University of Technology
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Karolinska Institutet
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Umeå University