Abstract
BACKGROUND: Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs(1)) were associated with cancer in cross-sectional studies. Whether SIBLINGs associate with preclinical disease is unknown. METHODS: A retrospective longitudinal case control study was performed to determine the association of SIBLINGs and prostate-specific antigen (PSA) with preclinical disease. Paired serum samples from 109 cancer-free Baltimore Longitudinal Study on Aging participants were divided into those that were either most distal or proximal to diagnosis (cases) or censored (controls). Dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP), osteopontin (OPN), and PSA were measured by immunoassay and dichotomized into low or high based on their respective cut-off values. Associations of time to diagnosis or death, modeled as disease-free survival (DFS) or overall survival (OS), were assessed using Kaplan Meier and Cox proportional hazard survival estimates on individual and aggregated biomarkers in distal or proximal sets separately. Models were adjusted for relevant covariates. A false discovery rate analysis assessed significance of hazard ratios (HRs) in sets. RESULTS: Biomarkers/aggregates identified as true discoveries for DFS included DSPP + PSA, OPN + PSA, DSPP + BSP + PSA, DSPP + OPN + PSA, where unadjusted distal HRs ranged between 11 and 27 and after adjusting for age from 7 to 15, while proximal HRs ranged between 6 and 10 unadjusted and 5 to 12 after adjusting for age. For proximal OS, true discoveries included DSPP + BSP, DSPP + OPN, DSPP + BSP + OPN, and DSPP + OPN + PSA where unadjusted HRs ranged between 6 and 20 while age-adjusted HRs ranged between 5 and 12. CONCLUSIONS: These observations support SIBLINGs as biomarkers that associate with DFS and OS in prediagnosis samples.