A predictive equation to adjust for clinical variables in soluble mesothelin-related protein (SMRP) levels

Abstract Background: Malignant mesothelioma (MM) is an aggressive pleural tumor which is difficult to diagnose in its early stages. Thus, biomarkers for MM including soluble mesothelin-related protein (SMRP) are currently an area of intense research interest. However, SMRP is affected by several factors other than malignancy which need to be taken into account in the individual patient. This study aimed to evaluate factors required to adjust SMRP levels for such variables and produce a useful prediction equation for clinical application. Methods: Serum SRMP levels were measured in 535 subjects formerly exposed to asbestos and silica, including many with asbestos-related disorders (ARDs). Linear regression analyses were used to quantify the strength and “direction” of the relationship between SMRP and several independent variables, and 2×2 tables were used to determine the diagnostic accuracy of SMRP levels, taking into account clinical variables. Results: SMRP levels were affected by age and glomerular filtration rate (GFR), which were strong confounders in this study. Body mass index (BMI) was also an initial confounder but lost significance after other factors were taken into account. SMRP was also affected by smoking. Poor sensitivity (15.1%) for SMRP values among subjects with non-malignant asbestos-related disorders was found when compared to currently healthy subjects with a history of asbestos exposure. Conclusions: The present study proposes an equation based on age and GFR to improve diagnostic accuracy of SMRP. The poor sensitivity of SMRP found in this study suggests that further work is needed to find new candidate biomarkers for diagnosing early stage MM.