The role of circulating protein and metabolite biomarkers in the development of pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis

Swati Kumar; Ralph J. Santos; Andrew J. McGuigan; Urvashi Singh; Peter Johnson; Andrew T. Kunzmann; Richard C. Turkington

doi:10.1158/1055-9965.EPI-21-0616

The role of circulating protein and metabolite biomarkers in the development of pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis

Swati Kumar, Ralph J. Santos, Andrew J. McGuigan, Urvashi Singh, Peter Johnson, Andrew T. Kunzmann, Richard C. Turkington^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development.

Methods
A literature search until August 2020 in MEDLINE, EMBASE and Web of Science was performed. Studies were included if they assessed circulating blood, urine or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk.

Results
A total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC (n=4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22). Additionally, an inverse association was seen with pyridoxal 5′-phosphate (PLP) levels (n=4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched chain amino acids with PDAC risk but due to differences in measures reported, a meta-analysis could not be performed.

Conclusions
Our pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC. Impact: Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.

Original language	English
Pages (from-to)	1090-1102
Journal	American Journal of Cancer
Volume	31
Issue number	5
Early online date	22 Nov 2021
DOIs	https://doi.org/10.1158/1055-9965.EPI-21-0616
Publication status	Published - 01 May 2022

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10.1158/1055-9965.EPI-21-0616Licence: CC BY

The role of circulating protein and metabolite biomarkers in the development of pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis
Copyright 2021 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.22 MBLicence: CC BY

Investigating the role of the immune landscape in pancreatic ductal adenocarcinoma
McGuigan, A. J. (Author), Turkington, R. (Supervisor) & Coleman, H. (Supervisor), Jul 2025
Student thesis: Doctoral Thesis › Doctor of Medicine

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Proteomics and metabolomics-based identification of novel treatment strategies in pancreatic ductal adenocarcinoma
Kumar, S. (Author), Turkington, R. (Supervisor) & Kerr, E. (Supervisor), Dec 2022
Student thesis: Doctoral Thesis › Doctor of Philosophy
Risk prediction of pancreatic cancer using clinical risk factors and biomarkers
Santos, R. J. B. (Author), Kunzmann, A. (Supervisor), Coleman, H. (Supervisor) & Cairnduff, V. (Supervisor), Jul 2024
Student thesis: Doctoral Thesis › Doctor of Philosophy

Cite this

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title = "The role of circulating protein and metabolite biomarkers in the development of pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis",

abstract = "BackgroundPancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development.MethodsA literature search until August 2020 in MEDLINE, EMBASE and Web of Science was performed. Studies were included if they assessed circulating blood, urine or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk.ResultsA total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC (n=4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22). Additionally, an inverse association was seen with pyridoxal 5′-phosphate (PLP) levels (n=4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched chain amino acids with PDAC risk but due to differences in measures reported, a meta-analysis could not be performed.ConclusionsOur pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC. Impact: Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.",

author = "Swati Kumar and Santos, {Ralph J.} and McGuigan, {Andrew J.} and Urvashi Singh and Peter Johnson and Kunzmann, {Andrew T.} and Turkington, {Richard C.}",

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doi = "10.1158/1055-9965.EPI-21-0616",

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T1 - The role of circulating protein and metabolite biomarkers in the development of pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis

AU - Kumar, Swati

AU - Santos, Ralph J.

AU - McGuigan, Andrew J.

AU - Singh, Urvashi

AU - Johnson, Peter

AU - Kunzmann, Andrew T.

AU - Turkington, Richard C.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - BackgroundPancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development.MethodsA literature search until August 2020 in MEDLINE, EMBASE and Web of Science was performed. Studies were included if they assessed circulating blood, urine or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk.ResultsA total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC (n=4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22). Additionally, an inverse association was seen with pyridoxal 5′-phosphate (PLP) levels (n=4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched chain amino acids with PDAC risk but due to differences in measures reported, a meta-analysis could not be performed.ConclusionsOur pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC. Impact: Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.

AB - BackgroundPancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development.MethodsA literature search until August 2020 in MEDLINE, EMBASE and Web of Science was performed. Studies were included if they assessed circulating blood, urine or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk.ResultsA total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC (n=4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22). Additionally, an inverse association was seen with pyridoxal 5′-phosphate (PLP) levels (n=4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched chain amino acids with PDAC risk but due to differences in measures reported, a meta-analysis could not be performed.ConclusionsOur pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC. Impact: Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.

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DO - 10.1158/1055-9965.EPI-21-0616

M3 - Article

SN - 0008-5472

VL - 31

SP - 1090

EP - 1102

JO - American Journal of Cancer

JF - American Journal of Cancer

IS - 5

ER -

The role of circulating protein and metabolite biomarkers in the development of pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis

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Student theses

Investigating the role of the immune landscape in pancreatic ductal adenocarcinoma

Proteomics and metabolomics-based identification of novel treatment strategies in pancreatic ductal adenocarcinoma

Risk prediction of pancreatic cancer using clinical risk factors and biomarkers

Cite this