Inflammation-immune‑nutrition biomarkers and PSA variability: A population‑based study on the clinical potential of the CALLY index

Prostate cancer (PCa) is the second leading cause of cancer-associated mortalities worldwide. Prostate-specific antigen (PSA) testing is pivotal for screening for PCa, despite its limited specificity due to confounding factors such as inflammation and nutritional status. The present study investigated the association between the C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index and PSA levels in a population without PCa. Using data from 5,320 men aged ≥40 years from the 2003-2010 national health and nutrition examination survey cycles, weighted multivariate linear regression and restricted cubic spline analyses were conducted. The findings revealed a significant inverse linear association: For each unit increase in the CALLY index, the PSA levels decreased by 0.09 ng/ml (β coefficient, -0.09; 95% confidence interval, -0.16 to -0.02). This association persisted across individuals with different ages, smoking habits and comorbidity subgroups. By integrating markers of systemic inflammation (such as the CRP levels), nutritional status (such as the albumin levels) and adaptive immunity (such as the lymphocyte counts), the CALLY index may refine the interpretation of the PSA levels and reduce the number of PCa false positive results, which occur due to subclinical inflammation. The present cross-sectional study highlighted that the CALLY index, as an adjunct biomarker, may have increased the accuracy of the screening for PCa. However, due to the cross-sectional design of the present study, causal associations cannot be established, and clinical applicability should be interpreted with caution. Therefore, further longitudinal and experimental studies are needed to elucidate the causal pathways and underlying mechanisms that link the CALLY index to the PSA levels.