Urinary metabolite prognostic biomarker panel for pancreatic ductal adenocarcinomas

Luke Hipperson; William J Hadden; Christopher B Nahm; Anthony J Gill; Jaswinder S Samra; Anthony Dona; Anubhav Mittal; Sumit Sahni

doi:10.1016/j.bbagen.2021.129966

Urinary metabolite prognostic biomarker panel for pancreatic ductal adenocarcinomas

Biochim Biophys Acta Gen Subj. 2021 Nov;1865(11):129966. doi: 10.1016/j.bbagen.2021.129966. Epub 2021 Jul 27.

Authors

Luke Hipperson¹, William J Hadden², Christopher B Nahm³, Anthony J Gill⁴, Jaswinder S Samra⁵, Anthony Dona⁶, Anubhav Mittal⁷, Sumit Sahni⁸

Affiliations

¹ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Kolling Institute of Medical Research, University of Sydney, St Leonards, Sydney, Australia.
² Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Kolling Institute of Medical Research, University of Sydney, St Leonards, Sydney, Australia; The Ottawa Hospital, Department of Orthopaedic Surgery, Canada.
³ Kolling Institute of Medical Research, University of Sydney, St Leonards, Sydney, Australia; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Australia; Western Clinical School, Faculty of Medicine and Health, University of Sydney, Australia.
⁴ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Kolling Institute of Medical Research, University of Sydney, St Leonards, Sydney, Australia; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia; NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
⁵ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia.
⁶ Kolling Institute of Medical Research, University of Sydney, St Leonards, Sydney, Australia.
⁷ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia. Electronic address: anubhav.mittal@sydney.edu.au.
⁸ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Kolling Institute of Medical Research, University of Sydney, St Leonards, Sydney, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia. Electronic address: sumit.sahni@sydney.edu.au.

PMID: 34329704
DOI: 10.1016/j.bbagen.2021.129966

Abstract

Background: Patients with pancreatic ductal adenocarcinoma (PDAC) have a very low survival rate and surgical resection is the only curative intent treatment available. However, the majority of patients relapse after surgery and identification of biomarkers for accurate prognostication of PDAC patients is required. We have recently identified a six biomarker (i.e., trigonelline, glycolate, hippurate, creatine, myoinositol and hydroxyacetone) urinary metabolite panel with very high potential to diagnose PDAC (Int J Cancer 2021;148:1508-18). This study aimed to assess the prognostic ability of these previously identified diagnostic metabolites in the urine of PDAC patients.

Methods: Metabolite data from 88 PDAC patients was statistically assessed for their prognostic ability.

Results: A panel of three metabolites (i.e., trigonelline, hippurate and myoinositol) was able to stratify patients with good- or poor-prognosis based on overall survival. The PDAC patients with abnormal levels of 2 or more metabolites in their urine demonstrated significantly lower survival compared to patients with abnormal levels of one or less metabolites.

Conclusion: These results demonstrate that the selected three metabolite panel could be used to stratify patients based on their prognostic outcomes and if independently validated may lead to the development of a urinary prognostic biomarker test for PDAC.

General significance: This study highlights the potential of using ¹H-nuclear magnetic resonance spectroscopy for the identification of novel metabolites which can prognosticate cancer patients.

Keywords: (1)H NMR; Metabolomics; Pancreatic ductal adenocarcinoma; Prognostic biomarkers; Urinary metabolites.

MeSH terms

Aged
Biomarkers, Tumor / metabolism
Biomarkers, Tumor / urine*
Carcinoma, Pancreatic Ductal / diagnosis*
Carcinoma, Pancreatic Ductal / metabolism
Carcinoma, Pancreatic Ductal / urine
Female
Humans
Male
Middle Aged
Pancreatic Neoplasms / diagnosis*
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / urine

Substances

Biomarkers, Tumor