Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer

Our plain-English summary of Clinical significance of serum mesothelin in patients with mesothelioma and lung cancer, by A. Cristaudo, R. Foddis, A. Vivaldi, et al (Clinical Cancer Research, 2007).

The study

• Authors: A. Cristaudo, R. Foddis, A. Vivaldi, G. Guglielmi, N. Dipalma, R. Filiberti, M. Neri, M. Ceppi, M. Paganuzzi, G.P. Ivaldi, M. Mencoboni, P.A. Canessa, N. Ambrosino, A. Chella, L. Mutti, R. Puntoni
• Journal: Clinical Cancer Research
• Published: 2007;13(17):5076-81
• Cited by: 127 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: High levels of serum-soluble mesothelin family proteins (SMRP) have been found to be associated with malignant mesothelioma (MM), but not lung cancer (LC). To verify the clinical role of this marker for both these tumors, we tested serum SMRP in the largest population of thoracic cancers ever assembled.

Experimental Design: SMRP blood concentrations were measured in 107 patients with MM, 215 patients with LC, 130 patients with benign respiratory diseases (BRD), and 262 controls. Statistical comparison between mean serum SMRP levels in all groups was done and receiver operating characteristic curves were constructed to evaluate the performance of this marker.

Results: SMRP levels were significantly higher in patients with MM and LC than in patients with benign respiratory diseases and controls (P < 0.001). The area under the receiver operating characteristic curve for serum SMRP discriminating MM and controls was 0.77 (95% confidence interval, 0.71-0.83), with a best cutoff of 1.00 nmol/L (sensitivity, 68.2%; specificity, 80.5%). In both MM and LC, serum SMRP levels did not differ significantly between early and late stages. High SMRP levels proved to be an independent negative prognostic factor in patients with MM.

Conclusions: Our data confirm that serum SMRP is a promising marker for the diagnosis, prognosis, and clinical monitoring of MM. We found that serum SMRP dosage may prove helpful in LC diagnosis as well. These data may also have positive repercussions on secondary preventive medical strategies for workers previously exposed to asbestos.

In plain English

This Italian study measured a blood marker, soluble mesothelin-related peptides (SMRP), in 107 patients with malignant mesothelioma, 215 with lung cancer, 130 with benign respiratory diseases and 262 controls. Of the controls, 203 were workers previously exposed to asbestos. SMRP was significantly higher in mesothelioma than in benign disease, controls or lung cancer. It was not correlated with asbestos exposure. Against controls, a cutoff of 1.00 nmol/L identified mesothelioma with 68.2% sensitivity and 80.5% specificity. Levels did not differ significantly between early and late mesothelioma stages. In a survival analysis of 52 mesothelioma patients, SMRP above 1 nmol/L was an independent predictor of poorer survival (hazard ratio 1.62; 95% CI 1.10-2.39). Lung cancer patients also had higher levels than benign disease patients and controls, but at that cutoff the test detected only 33.5% of lung cancers. The authors concluded that high SMRP was an independent negative prognostic factor in mesothelioma and could help clinical and preventive purposes. They also concluded that it could not be proposed for lung cancer screening.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Comparison of blood marker (serum SMRP) levels across patient groups and controls, with diagnostic accuracy analysis and survival follow-up of the mesothelioma patients
• Who was studied: 107 patients with malignant mesothelioma, 215 with lung cancer, 130 with benign respiratory diseases and 262 controls, from two Italian regions (Tuscany and Liguria); study dates not given
• Exposure: Asbestos exposure was assessed by questionnaire. 203 of the 262 controls were workers previously exposed to asbestos for at least a decade. No fiber types were named.
• Main results:
  • SMRP levels were not correlated with age or asbestos exposure in any group
  • Mesothelioma patients had significantly higher SMRP than patients with benign respiratory diseases or controls (P < 0.001)
  • Mesothelioma patients had significantly higher SMRP than lung cancer patients (P < 0.001)
  • Among mesothelioma patients, high SMRP concentrations were detected only in the epithelioid and mixed types
  • In mesothelioma patients, SMRP differences between early and late stages were not statistically significant
  • Mesothelioma versus controls: area under the ROC curve 0.77 (95% CI 0.71-0.83) for all stages, and 0.77 (95% CI 0.68-0.89) for stage I to II
  • Mesothelioma versus controls: best cutoff 1.00 nmol/L, with sensitivity 68.2% and specificity 80.5%
  • At the 1.00 nmol/L cutoff, the estimated positive predictive value was 0.35% and the negative predictive value 99.96%. These were based on an assumed mesothelioma rate in the asbestos-exposed population.
  • Mesothelioma versus lung cancer: area under the ROC curve 0.70 (95% CI 0.63-0.77)
  • None of the 392 subjects without a tumor (controls and benign respiratory disease patients) had SMRP above 2.4 nmol/L
  • Of 101 mesothelioma patients followed up, 69 (68.3%) died during the study period
  • Median survival of mesothelioma patients was 21.5 months with SMRP below 1 nmol/L and 9.8 months with SMRP above it (P < 0.001)
  • The multivariate (Cox) survival analysis included only the 52 mesothelioma patients with complete data on age, sex, histology, stage, platelet count and treatments
  • In that analysis, SMRP above 1 nmol/L was an independent predictor of poor survival in mesothelioma patients (HR 1.62; 95% CI 1.10-2.39; P = 0.02)
  • Lung cancer patients had significantly higher SMRP than patients with benign respiratory diseases (P = 0.001) or controls (P < 0.001)
  • SMRP levels did not differ significantly between lung cancer stages
  • Lung cancer versus benign respiratory diseases: area under the ROC curve 0.58 (95% CI 0.52-0.64)
  • Lung cancer versus controls: area under the ROC curve 0.62 (95% CI 0.56-0.68), specificity 80.2%, sensitivity 33.5%
• The authors' conclusion: The authors concluded that high SMRP can be considered an independent negative prognostic tool for patients with mesothelioma, and that the test could be helpful for both clinical and preventive purposes
• Limitations the authors state:
  • The authors stated that the test detected lung cancer poorly at the 1 nmol/L cutoff (33% sensitivity), so it could not be proposed for lung cancer screening
  • The authors stated that, even with high sensitivity and specificity, no such marker could reach a satisfactory positive predictive value for a rare tumor such as mesothelioma

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelin, Mesothelioma, Lung Cancer, Soluble Mesothelin-Related Peptides (SMRP), confidence interval, Prognosis.

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• Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment — B.D. Grigoriu, A. Scherpereel, et al. (2007)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma — J. Creaney, D. Yeoman, et al. (2008)
• Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma — J. Creaney, N.J. Olsen, et al. (2010)

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