The Effect of Clinical Covariates on the Diagnostic and Prognostic Value of Soluble Mesothelin and Megakaryocyte Potentiating Factor

Hollevoet, Kevin; Nackaerts, Kristiaan; Thas, Olivier; Thimpont, Joël; Germonpré, Paul; Vuyst, Paul De; Bosquee, Lionel; Legrand, Catherine; Kellen, Eliane; Kishi, Yoshiro; Delanghe, Joris; Meerbeeck, Jan P. van

doi:10.1378/chest.11-0129

Cited by 42 publications

(55 citation statements)

References 27 publications

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“…Concentrations of mesothelin in serum of MM patients are significantly higher than those of healthy individuals [15][16][17][18][19][20][21].…”

Section: Diagnostic Performancementioning

confidence: 99%

“…Furthermore, it has been demonstrated that its levels in patients with MM are significantly higher when compared with those of patients with other cancers (including lung cancer) or other inflammatory lung or pleural diseases [16][17][18][19][20][21][22][23][24][25][26][27].…”

Section: Diagnostic Performancementioning

confidence: 99%

“…Table 1 shows sensitivity, specificity and the area under the receiver operating characteristic curves (AUC) at several cutoff points. The wide range of the reported ''optimal'' thresholds depends on the different study populations and the effect of patient characteristics [21].…”

Section: Diagnostic Performancementioning

confidence: 99%

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Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

et al. 2012

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Malignant mesothelioma (MM) is an aggressive tumour with poor prognosis whose early diagnosis is difficult. Mesothelin, megakaryocyte potentiating factor (MPF) and osteopontin have attracted attention as biomarkers. The aim of the present review is to provide an overview regarding these candidate biomarkers for MM, and discuss their potential role in today's clinical practice.Mesothelin and MPF have good specificity but sub-optimal sensitivity for detection of MM, being negative both in the sarcomatoid histological sub-type and in almost half of epithelioid mesothelioma, especially in the early stages. Osteopontin is a marker of the duration of asbestos exposure, but lacks specificity for mesothelioma. Several patient characteristics influence the diagnostic accuracy of biomarkers and make the establishment of the ''optimal'' diagnostic threshold difficult. Mesothelin and MPF have proved useful in assessing response to treatment. Combining different markers together may lead to an improvement in diagnostic accuracy, but there is still need for research in this area. Extensive validation and further research is required to improve the use of serum markers in mesothelioma management. In the near future, their application in clinical practice is probably in monitoring response to therapy, rather than in guiding diagnostic decisions and risk assessment of asbestos-exposed populations.

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“…Concentrations of mesothelin in serum of MM patients are significantly higher than those of healthy individuals [15][16][17][18][19][20][21].…”

Section: Diagnostic Performancementioning

confidence: 99%

Section: Diagnostic Performancementioning

confidence: 99%

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Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

et al. 2012

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“…SMRP may be mildly to moderately increased in benign cases such as those with asbestos exposure, arterial hypertension, congestive heart failure or renal insufficiency 36 . Serum SMRP levels may be affected by age, weight (body mass index < 25), high glucose levels, smoking and a history of malignancy or asbestos-related pleural involvement [49][50][51][52] . Given the fact that asbestos is the main causative factor for mesothelioma and asbestos workers are the most threatened population group with a significantly increased risk for development of the disease, they are suitable for monitoring and examinations, including assessment of the clinical significance of mesothelin, in particular with respect to early detection of pleural mesothelioma.…”

Section: Introductionmentioning

confidence: 99%

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

Jakubec¹,

Pelclová²,

Smolková³

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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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.

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“…In 2007, serum mesothelin has been reported, for the first time, as a prognostic marker in MPM: high soluble mesothelin level significantly correlates with shorter survival, leading to a poor prognosis (12). Its prognostic value has been strongly debated: many following studies confirmed this association (13-15) but others did not endorse serum mesothelin prognostic significance (26,87). While a recent meta-analysis performed on 579 MPM patients further corroborates the inverse association of serum SMRP concentration with the OS (16).…”

Section: Clinical Implications Of Overexpressed Genes In Mpmmentioning

confidence: 99%

Overexpressed genes in malignant pleural mesothelioma: implications in clinical management

2018

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Malignant pleural mesothelioma (MPM) is a very aggressive cancer poorly responsive to current therapies. MPM patients have a very poor prognosis with a median survival of less than one year from the onset of symptoms. The biomarkers proposed so far do not lead to a sufficiently early diagnosis for a radical treatment of the disease. Thus, the finding of novel diagnostic and prognostic biomarkers and therapeutic targets is needed. Gene overexpression has been frequently associated with a malignant phenotype in several cancer types; therefore the identification of overexpressed genes may lead to the detection of novel prognostic or diagnostic marker and to the development of novel therapeutic approaches, based on their inhibition. In the last years, several overexpressed genes have been identified in MPM through gene expression profiling techniques: among them it has been found a group of 51 genes that resulted overexpressed in more than one independent study, revealing their consistency among studies. This article reviews the clinical implications of confirmed overexpressed genes in MPM described so far in literature.

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The Effect of Clinical Covariates on the Diagnostic and Prognostic Value of Soluble Mesothelin and Megakaryocyte Potentiating Factor

Cited by 42 publications

References 27 publications

Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

Effectiveness of mesothelin family proteins and osteopontin for malignant mesothelioma: Table 1–

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

Overexpressed genes in malignant pleural mesothelioma: implications in clinical management

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