Significance of serum mesothelin in an asbestos-exposed population in the Czech Republic

Abstract

Aims. Pleural mesothelioma is a highly aggressive and difficult-to-treat form of cancer induced by asbestos in 80-90% of cases. The population group most at risk of the condition are asbestos-exposed workers. Mesothelin or soluble mesothelin-related protein (SMRP) is studied as a potential marker of mesothelioma in the at-risk population. Methods. The study comprised 239 subjects with a mean duration of occupational exposure to asbestos of 19.9 years. In all of them, a complete medical history was taken, focused on exposure duration and a physical examination, a chest X-ray or other imaging investigations and a lung function test were performed. Their serum SMRP levels were measured and biopsy samples were taken to diagnose pleural disease. Based on the above examinations, the subjects were classified into subgroups and serum SMRP concentrations were statistically analyzed with respect to individual parameters. Results. In asbestos-exposed individuals, mesothelin levels were significantly higher in those with pathological X-ray findings than in those with normal X-ray results (0.78 ± 0.63 vs. 0.50 ± 0.35, P<0.0001). The group of patients with benign disease had statistically significantly higher mesothelin levels than those with normal X-ray findings (0.755 ± 0.543 vs. 0.50 ± 0.35, P<0.001). In the group with present malignant processes, mesothelin levels were higher than in individuals with benign disease (1.19 ± 0.89 vs. 0.76 ± 0.54, P=0.015). Only a weak correlation was found between mesothelin levels and asbestos exposure duration. There were relatively high sensitivity and high specificity (75% and 90.6%, respectively) of serum mesothelin for pleural mesothelioma. However, given the small number of mesothelioma cases in the group, the results cannot be considered as statistically significant. Conclusions. In persons followed up for asbestos exposure, increased mesothelin levels signalize pathological processes in the chest and correlate with severity of the disease. The study suggests that mesothelin cannot be considered a reliable marker for the early stage of malignant degeneration of pleural disease but only an additional criterion for examination of the followed-up individuals.

Mesothelin (MSLN) methylation and soluble mesothelin-related protein levels in a Chinese asbestos-exposed population

“…Furthermore, the relationship between SMRP values and asbestos exposure duration was examined in subjects occupationally exposed to asbestos. Our results support that there is no or weak correlation between SMRP levels and asbestos exposure duration [4,19,27]. So far, SMRP is not a desirable biomarker to discriminating the subjects exposed to asbestos from those without asbestos exposure, because the SMRP values were independent of the estimated exposure levels.…”

“…However, it was not feasible to discriminate healthy asbestos-exposed individuals from those with benign pleural and pulmonary disorders by using SMRP measurement. Previous studies indicated the possibility of SMRP to screen cases with pleural and lung disorders in asbestos-exposed population, although the efficiency of SMRP-based screening approach needs further investigation in prospective cohort studies [6,8,19,[26][27][28]. In these studies, few had evaluated the potential confounders influencing the value of SMRP [26][27][28].…”

“…Serum SMRP concentrations were assayed with a commercial ELISA kit (MESOMARK, Fujirebio Diagnostics) according to the manufacturer's guidelines and SMRP values in the tested samples was determined using 6-point calibration curve (range 0-32 nM) as previously described [4,19]. The value below the limit of detection (LOD) was reported as 0.3 nM for statistic purpose in that the LOD for SMRP assay is 0.3 nM [5,7,9].…”

Validity of mesothelin in occupational medicine practice

“…However, the difference is not significant given the large confidence intervals (in particular for sensitivity, PPV, positive LR and DOR, as it has been already discussed), mainly due to the low number of MM cases in the present study. Numerous other studies have confirmed the diagnostic yield and convenience of the use of SMRP concentrations for the diagnosis of MM, often recommending consideration of further diagnostic steps in case of positive results [5,13,[27][28][29][30]. For instance, in a recent review, Cristaudo et al have stated that SMRP levels seem to be the most adequate biomarker for MM in spite of the fact that they may be genetically and clinically affected [2].…”

Bioanalytical Techniques for Detecting Biomarkers of Response to Human Asbestos Exposure

“…A recent review reported a meta analysis of 30 publications to determine the sensitivity and specificity of SMRP as a biomarker of mesothelioma [90]. Studies on occupational exposure to asbestos in the Czech Republic revealed distinguishing serum levels of SMRP in which exposed subjects with benign disease had higher levels than normal subjects but lower levels than subjects with MM as determined by CXRs [91]. An additional study from Australia used a sandwich ELISA with two monoclonal antibodies (OV569 and 4H3) comparing a non-exposed control group of 28 controls with 40 asbestos exposed (Table 1) [55].…”