Increased plasma concentrations of acyl-coenzyme A binding protein (ACBP) predict future lung cancer development in smokers at risk of cardiovascular disease
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Acyl-coenzyme A binding protein (ACBP), encoded by the diazepam binding inhibitor (DBI) gene, is a tissue stress hormone the circulating concentrations of which increase with age, obesity and cardiometabolic risk factors. Elevated plasma ACBP/DBI levels have recently been associated with future cardiovascular and cancer risk, particularly lung cancer (LC), independent of smoking status. METHODS: To validate ACBP/DBI as a biomarker of LC risk, we analyzed plasma samples from four independent cohorts within the PREVALUNG EU consortium: healthy volunteers, the FLEMENGHO cohort of smokers at cardiovascular risk, the ROBINSCA cohort of smokers at risk of cardiovascular disease (CVD) who later developed LC, and the PREVALUNG cohort of smokers with manifest CVD. ACBP/DBI concentrations were quantified using the Olink proximity extension assay, benchmarked against ELISA and Somascan platforms. RESULTS: Across cohorts, individuals who subsequently developed LC exhibited higher baseline ACBP/DBI levels than cancer-free controls. In smokers at cardiovascular risk but without manifest CVD, ACBP/DBI discriminated future LC cases with an AUC-ROC of 0.68 (unadjusted) and 0.73 (adjusted for age, sex, BMI and smoking). Elevated ACBP/DBI levels predicted LC occurrence over more than a decade of follow-up. In contrast, among smokers with established CVD, ACBP/DBI levels were uniformly high regardless of cancer outcome. CONCLUSIONS: These findings independently validate ACBP/DBI as a circulating biomarker of future LC development in at-risk individuals. Clinically, ACBP/DBI quantification could refine risk-adapted lung cancer screening strategies, guiding the frequency of low-dose CT scans and identifying candidates for preventive interventions, including potential ACBP/DBI-neutralizing therapies.
Source: Molecular Cancer
Institutions: Inserm, Université Paris-Saclay, Institut Gustave Roussy, La Ligue Contre le Cancer, Institut Universitaire de France, Université Paris Cité, Sorbonne Université, Centre de Recherche des Cordeliers, Centre National de la Recherche Scientifique, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse, Aix-Marseille Université, Hôpital Nord, Hôpital Marie Lannelongue, KU Leuven, Erasmus MC, Immunologie anti-tumorale et immunothérapie des cancers, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,090
Awards: G1190173965, G1846858737, G1912211089, G1963894250, G2037922406, G2161503289, Lung cancer prevention and interception, Biomarkers affecting the transition from cardiovascular disease to lung cancer: towards stratified interception., G3116448791, Microbiota-controlled trafficking of immunosuppressive intestinal T cells into cancer, G434337789, 4-IN THE LUNG RUN: towards INdividually tailored INvitations, screening INtervals, and INtegrated co-morbidity reducing strategies in lung cancer screening, G4532900596, G4656594441, G4707887143, G4990482369, G540687550, Microbiota-centered interventions to solve antibiotics-induced primary resistance to immune checkpoint inhibitors, G5468290041, New and more individualised population-based screening for cardiovascular disease; from a RCT including selfassessments, primary care and coronary artery calcification score to modelling risk-benefit, G5674527738, G5851709705, G6318841463, G7080048889, G7255431040, G816800923, G82931992, Université de Paris, G8903562841
OpenAlex ID: W4416672780