External Validation of Plasma Glycosaminoglycans as Biomarkers to Improve Lung Cancer Risk Stratification

Davies, MPA ORCID: 0000-0002-7609-4977, Field, JK ORCID: 0000-0003-3951-6365 and Gatto, F (2025) External Validation of Plasma Glycosaminoglycans as Biomarkers to Improve Lung Cancer Risk Stratification Cancer Epidemiology Biomarkers and Prevention, 34 (7). pp. 1219-1225. ISSN 1055-9965, 1538-7755

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Abstract

Background: Lung cancer screening excludes individuals not considered at an increased risk for lung cancer, as predicted by risk models like the Liverpool Lung Project version 3 (LLPv3). In this study, we sought to validate whether plasma glycosaminoglycan profiles (GAGomes) could predict lung cancer independent of LLPv3 and other prespecified comorbidities. Methods: In this retrospective cohort-based case-control study, we included patients who were suspected of having lung cancer at baseline and were either diagnosed with lung cancer (cases) or remained cancer-free for 5 years after baseline (controls). Plasma GAGomes were measured at baseline and used to compute a prespecified GAGome score to discriminate lung cancer from controls. We then applied multivariable Bayesian logistic regression to evaluate the likelihood that 7 LLPv3 predictors or 14 comorbidities had an effect on the GAGome score. We tested the independence of the GAGome score from LLPv3-predicted 5-year risk using the likelihood ratio test and assessed whether it improved lung cancer risk prediction in a set equivalent to an LLPv3-predicted 5-year risk of ≥1.51%. Results: We included 653 lung cancer and 653 controls. The AUC of the GAGome score was 0.63 (95% confidence interval, 0.62-63). None of the LLPv3 predictors or comorbidities were compatible with a significant effect on the score. The GAGome score was independent of LLPv3 (P < 0.001) and improved its sensitivity (72% vs. 69%) and specificity (61% vs. 59%). Conclusions: Plasma GAGomes identified additional lung cancer cases beyond those predicted by LLPv3 alone. Impact: GAGomes could improve risk-stratified lung cancer if validated in a screening population.

Item Type:	Article
Uncontrolled Keywords:	Humans, Lung Neoplasms, Glycosaminoglycans, Risk Assessment, Risk Factors, Case-Control Studies, Retrospective Studies, Aged, Middle Aged, Female, Male, Early Detection of Cancer, Biomarkers, Tumor
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	19 Jun 2025 07:47
Last Modified:	28 Feb 2026 01:06
DOI:	10.1158/1055-9965.EPI-24-1537
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3193315
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