Soluble Mesothelin-related Protein Research Articles

Mesothelin family proteins and diagnosis of mesothelioma: analytical evaluation of an automated immunoassay and preliminary clinical results

Studies have suggested that soluble mesothelin-related protein (SMRP) can be used as a serum marker of malignant mesothelioma. We assessed the analytical performance of the Mesomark (Fujirebio Diagnostic) two-step ELISA on an automated analyser and performed a preliminary clinical evaluation. The precision of the assay and the in vitro effect of interfering substances on SMRP concentrations were investigated. The serum marker was analysed in 109 healthy subjects never exposed to asbestos, 26 healthy subjects exposed to asbestos, 33 patients with asbestosis, 33 with asbestos-related pleural plaques, 10 with non-malignant pleural diseases, 30 with lung cancer and 24 with histological diagnosis of pleural mesothelioma. Using the International Mesothelioma Interest Group classification, there were nine stage IV, two stage III, four stage II and nine stage I patients. SMRP concentrations of 4.75, 11.0 and 14 nmol/mL showed a total imprecision of 3.5%, 3.1% and 3.8%. The detection limit was 0.035 nmol/mL; the mean SMRP concentration of 0.63 nmol/mL was associated with a coefficient of variation of 10%. There was no effect (p>0.05) of interfering substances. Serum samples from patients with established pleural mesothelioma had significantly higher (p<0.05) concentrations of SMRP than control healthy and patient groups. SMRP measured on automated systems could be useful for the diagnosis of mesothelioma in routine clinical practice.

156 Soluble mesothelin-related protein (SMRP) is a useful biomarker for malignant mesothelioma in Japan

156 Soluble mesothelin-related protein (SMRP) is a useful biomarker for malignant mesothelioma in Japan

152 Pre-diagnostic soluble mesothelin related protein, CA125, CYFRA 21-1 and risk of mesothelioma: A case-control study

152 Pre-diagnostic soluble mesothelin related protein, CA125, CYFRA 21-1 and risk of mesothelioma: A case-control study

150 Predictive and/or diagnostic significance of serum soluble mesothelin related proteins (SMR) in asbestos-related pleural malignant mesothelioma: Follow-up of a large population of workers previously exposed to asbestos

150 Predictive and/or diagnostic significance of serum soluble mesothelin related proteins (SMR) in asbestos-related pleural malignant mesothelioma: Follow-up of a large population of workers previously exposed to asbestos

Mesothelin Variant 1 Is Released from Tumor Cells as a Diagnostic Marker

The mesothelin family comprises (at least) three variants and includes the precursor for megakaryocyte potentiating factor (MPF). Assaying soluble mesothelin-related protein (SMRP) molecules in serum and other body fluids from patients with certain cancers can provide diagnostically useful information. We have constructed fusion proteins of mesothelin variants 1, 2, and 3, made monoclonal antibodies, and investigated the binding specificity of these and three previously generated monoclonal antibodies to each of the three mesothelin variants. According to flow cytometry, the molecule that is most frequently expressed at the surface of cells from ovarian carcinomas and certain other tumors is mesothelin variant 1. Similarly, SMRP released into ascites from a patient with ovarian carcinoma was shown to have a molecular weight of approximately 40 kDa and, according to sequencing, to be variant 1. A published sandwich ELISA was shown to detect variants 1 and 3 and to be much more sensitive than a newly constructed ELISA, which detects only variant 3, the former being positive in 28 of 41 (68%) sera from patients with ovarian cancer as compared with 6 of 41 sera (15%). A standard curve was constructed to measure SMRP with a limit of detection of 200 pg/mL to facilitate future quantitative studies.

Soluble Mesothelin Related Protein in Mesothelioma

The worldwide incidence of malignant mesothelioma is increasing. This is a highly aggressive asbestos-related tumor with a median survival of less than a year.1 Treatment options have been limited and have done little to extend the median survival, although some strategies, such as complete tumor resection in patients with early disease, seem promising.2,3 Serum markers have been useful for the clinical management of different cancers.4 Currently no serum markers are in routine use for the clinical management of patients with mesothelioma. We have therefore evaluated a newly described tumor marker, soluble mesothelin related protein (SMRP),5 in patients with mesothelioma. SMRP is a member of the mesothelin family of proteins. Little is known of the function of this family of proteins. Mesothelin itself is a 40kDa cell surface protein that is present on normal mesothelial cells and on some cancers including mesothelioma, ovarian, and pancreatic cancer.6 It is believed that alternative splicing of the mesothelin gene results in the production of SMRP, a putatively soluble protein with an N-terminal region identical to that of mesothelin but with a different C-terminal. Using a doubledeterminant enzyme-linked immunosorbent assay, SMRP has been detected in the serum of patients with ovarian cancer and in a few patients with other cancers5

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.

Mesothelin-family proteins and diagnosis of mesothelioma.

Mesothelioma is a highly aggressive tumour for which there are no reliable serum tumour markers. Identification of such a marker would be useful in diagnosis of mesothelioma and for monitoring responses to treatment and screening at-risk individuals. We assayed serum concentrations of soluble mesothelin-related proteins (SMR) using a double determinant (sandwich) ELISA in a blinded study of serum samples from 44 patients with histologically proven mesothelioma; 68 matched healthy controls, 40 of whom had been exposed to asbestos; and 160 patients with other inflammatory or malignant lung and pleural diseases. 37 (84%) of 44 patients with mesothelioma had raised concentrations of SMR at a serum dilution of 1/80, compared with three (2%) of 160 patients with other cancers or other inflammatory lung or pleural diseases, and with none of 28 controls who had not been exposed to asbestos. SMR concentrations correlated with tumour size and increased during tumour progression. Seven of the 40 asbestos-exposed individuals had increased serum concentrations of SMR; three of those seven developed mesothelioma and one developed lung carcinoma within 1-5 years. None of the 33 asbestos-exposed participants whose serum samples had normal concentrations of SMR and who were followed up over 8 years developed mesothelioma. Determination of SMR in serum could be a useful marker for diagnosis of mesothelioma and to monitor disease progression. It might also prove helpful for screening asbestos-exposed individuals for early evidence of mesothelioma.