Soluble Mesothelin-related Protein Levels Research Articles

Circulating SMRP and CA-125 before and after pleurectomy decortication for pleural mesothelioma.

Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin-related protein (SMRP) and cancer antigen 125 (CA-125) are established blood-based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD). Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post-operation, and (3) recurrence. Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow-up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA-125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease-free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA-125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA-125 across the study timepoints (p = 0.47). Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA-125 could be helpful in recognizing abdominal recurrences.

Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers

Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.

Krebs von den Lungen 6 (KL-6) is a novel diagnostic and prognostic biomarker in pleural mesothelioma

ObjectivesPleural mesothelioma (PM) is a rare disease with dismal outcome. Systemic treatment options include chemotherapy and immunotherapy, but biomarkers for treatment personalization are missing. The only FDA-approved diagnostic biomarker is the soluble mesothelin-related protein (SMRP). Krebs von den Lungen-6 (KL-6) is a human mucin 1 (MUC1) glycoprotein, which has shown diagnostic and prognostic value as a biomarker in other malignancies. The present study investigated whether KL-6 can serve as a diagnostic and/or prognostic biomarker in PM. Materials and methodsUsing a fully-automated chemiluminescence enzyme immunoassay (CLEIA) for KL-6 and SMRP, pleural effusion samples from 87 consecutive patients with PM and 25 patients with non-malignant pleural disorders were studied. In addition, KL-6 and SMRP levels were determined in corresponding patient sera, and in an independent validation cohort (n = 122). MUC1 mRNA and protein expression, and KL-6 levels in cell line supernatants were investigated in PM primary cell lines in vitro. ResultsPM patients had significantly higher KL-6 levels in pleural effusion than non-malignant controls (AUC 0.78, p < 0.0001). Among PM patients, levels were highest in those with epithelioid or biphasic histologies. There was a strong positive correlation between pleural effusion levels of KL-6 and SMRP (p < 0.0001). KL-6 levels in sera similarly associated with diagnosis of PM, however, to a lesser extent (AUC 0.71, p = 0.008). PM patients with high pleural effusion KL-6 levels (≥303 IU/mL) had significantly better overall survival (OS) compared to those with low KL-6 levels (HR 0.51, p = 0.004). Congruently, high tumor cell MUC1 mRNA expression in primary cell lines associated with prolonged corresponding patient OS (HR 0.35, p = 0.004). These findings were confirmed in an independent validation cohort. ConclusionThis is the first study demonstrating KL-6 as a potential novel liquid-based diagnostic and prognostic biomarker in PM.

Follow-up of Soluble Mesothelin-Related Protein Levels in Participants With Asbestos-Related Disorders

BackgroundAsbestos exposure is associated with the development of the cancer malignant mesothelioma (MM). Measurement of soluble mesothelin-related protein (SMRP) has been suggested as a method for detection of MM in its early stages. We prospectively examined SMRP levels in participants with asbestos exposure who are a group at a high risk of development of MM.MethodsThis study was a follow-up of our cohort of 322 asbestos-exposed participants. No further participants developed MM or malignancy over the study period. Mean follow-up time was 22.9 months.ResultsMean (standard deviation) SMRP levels at baseline and follow-up were 0.94 (0.79) and 0.91 (0.86) nmol/L (p = 0.1033), respectively. Mean SMRP levels of the healthy individuals exposed to asbestos at baseline was significantly lower than those of participants with asbestosis and pleural plaques alone; similar patterns were found on follow-up measurements. There was a statistically significant effect of age on serial SMRP measurements. Our study confirms higher levels in participants with nonmalignant asbestos-related disorders. Levels decreased in asbestos-related disorders other than asbestosis, where a small increase was observed. We did not detect any further cases of malignancy.ConclusionMonitoring programs for early detection of MM need to take into account increased SMRP levels found in benign asbestos-related diseases.

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

This study investigated the mesothelin (MSLN) methylation and its relationship with soluble mesothelin-related protein (SMRP) levels in participants stratified by asbestos exposure scenarios and benign asbestos-related diseases (ARDs). The presence of benign ARDs was confirmed through chest X-ray and the asbestos exposure history was obtained using a standardized questionnaire in this study, including 262 participants. Sera SMRP were measured using MESOMARK, and MSLN methylation in genomic DNA extracted from whole blood was detected by real-time methylation-specific PCR. Covariates were compared with SMRP concentrations using correlation analysis and the potential covariates affecting SMRP were determined by multiple linear regression analysis, and the distribution of methylation status was analyzed by Chi-square test. There was a trend toward elevation of SMRP values in healthy individuals exposed to asbestos as compared with those without asbestos exposure. The highest median level of SMRP was 1.3nM in subjects with asbestosis, followed by cases with pleura plaque and asbestosis (1.2nM), pleura plaque (0.9nM), healthy subjects with occupational exposure (0.9nM), non-occupational exposure (0.8nM), and mixed exposure (0.8nM). Within asbestosis cases, those with higher profusion scores had higher SMRP values than those with lower profusion scores (1.6 vs. 0.8nM). Based on multi-regression analysis, the trend toward elevation of SMRP remained significant in subjects with occupational exposure or in those with asbestosis, as compared with healthy subjects without exposure (p<0.01), although body mass index had an effect on SMRP (p<0.0001). Regardless of the differences in SMRP levels among these subgroups, MSLN methylation ranged from 80.5 to 92.5%, with no significant difference. The elevated level of SMRP in asbestosis with higher profusion scores could not be attributed to low MSLN methylation status. Our findings suggest that the elevation of SMRP is related to asbestos exposure and benign ARDs especially for cases with high profusion scores, which is independent of MSLN methylation.

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

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. 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. 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. 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.

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

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. 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. 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. 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 fi nd new candidate biomarkers for diagnosing early stage MM.

Soluble Mesothelin-related Protein Levels in Subjects With Malignant Mesothelioma

PP-30-155 Background/Aims: Malignant mesothelioma is a highly aggressive tumor associated mostly with asbestos exposure. Soluble mesothelin-related protein (SMRP) is a potential tumor marker for mesothelioma. The aim of this study was to determine the differences in serum SMRP levels at various phases of the disease before and during treatment. Methods: The study included all 78 subjects with mesothelioma treated at the Institute of Oncology, Ljubljana, between 2007 and 2009. According to the cumulative asbestos exposure, they were divided into 4 groups (nonexposed, low, medium, and high). Serum samples were collected in all subjects before the treatment and/or in different responses to treatment (complete response, partial response, stagnation, progressive disease). Serum SMRP levels were determined by enzyme-linked immunosorbent assay with 2 monoclonal antibodies. Results: Asbestos exposure was confirmed in 67 (85.9%) subjects. Only occupational exposure was observed in 32 subjects, only environmental in 12 subjects, and both occupational and environmental exposures in 23 subjects. The cumulative asbestos exposure was classified as low in 24, medium in 21, and high in 22 subjects. Mean serum SMRP was 5.75 nM before the treatment, 0.00 nM in complete response, 1.33 nM in partial response, 2.97 nM in stagnation, and 9.67 nM in progressive disease. The SMRP levels were significantly higher before the treatment compared to the stagnation, partial and complete responses to treatment (t = 2.49; P = 0.016), as well as in the progressive disease if compared to the stagnation, partial and complete responses to treatment (t 5.48; P 0.000). Conclusion: Asbestos exposure was confirmed in almost 86% of subjects with mesothelioma and among them, the exposure was low in 36% of subjects. As the findings of the study suggest that SMRP might be a useful tumor marker for detecting the progression of mesothelioma and tumor response to treatment, a thorough follow-up of a prospective cohort is needed.

Factors affecting soluble mesothelin related protein levels in an asbestos-exposed population

Soluble mesothelin-related protein (SMRP) is increased in the sera of patients with malignant mesothelioma (MM), and has been suggested as a diagnostic tool for MM in an asbestos exposed population. However, factors affecting SMRP concentrations in normal subjects and those with other asbestos related disorders have not been investigated in any large population based study. Five hundred and thirty-eight subjects with a history of asbestos exposure were studied. Age, height, weight, body mass index (BMI), serum creatinine and glucose, estimated glomerular filtration rate (eGFR) and lung function were compared with SMRP concentrations. The mean age [+/- standard deviation (SD)] of participants was 66.9 (+/-10.1) years, and mean (+/-SD) serum SMRP concentration was 0.91 (+/-0.67) nmol/L. SMRP values were inversely associated with weight (Pearson r=-0.1254, p=0.0036), BMI (Pearson r=-0.1594, p=0.0002), blood glucose (Pearson r=-0.1515, p=0.0004), single-breath carbon monoxide diffusing capacity (DLco) % predicted (Pearson r=-0.1847, p<0.0001), eGFR (Pearson r=-0.2835, p<0.0001) and single-breath carbon monoxide diffusing capacity per unit alveolar volume (DLco/VA)% predicted (Pearson r=-0.1872, p<0.0001) but were positively associated with age (Pearson r=0.2315, p<0.0001) and creatinine (Pearson r=0.3833, p<0.0001). This study has shown that demographic variables, physiological factors and lung function are associated with serum SMRP concentrations. Confounding factors should be considered when interpreting serum SMRP.

Polymorphisms in the putative micro-RNA-binding sites of mesothelin gene are associated with serum levels of mesothelin-related protein

BackgroundSerum mesothelin, also known as soluble mesothelin-related protein (SMRP), reportedly shows increased levels in epithelial-type malignant pleural mesothelioma, but sometimes also arrives at high values in healthy asbestos-exposed subjects.ObjectivesThis study...

Soluble mesothelin-related protein—A blood test for mesothelioma

Identification of tumor marker for mesothelioma (MM) might prove useful in diagnosis as well as for monitoring tumor in response to therapy and for screening at-risk individuals. We tested the hypothesis that soluble mesothelin-related protein (SMRP), a mesothelin family member, in the serum would be such a marker. Our data show that determination of SMRP in serum is a marker of MM with a sensitivity of sensitivity 83% and specificity 95% in the first 48 MM patients tested. Changes in serum SMRP levels parallel clinical course/tumor size and SMRP is elevated in 75% of patients at diagnosis. SMRP should also be useful for monitoring disease progression, and importantly, may prove useful for screening asbestos-exposed individuals for early MM.