Increased plasma concentrations of acyl-coenzyme A binding protein (ACBP) predict future lung cancer development in smokers at risk of cardiovascular disease.

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.