Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma

Our plain-English summary of Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma, by K. Hollevoet, K. Nackaerts, J. Thimpont, et al (American Journal of Respiratory and Critical Care Medicine, 2010).

The study

• Authors: K. Hollevoet, K. Nackaerts, J. Thimpont, P. Germonpré, L. Bosquée, P. De Vuyst, C. Legrand, E. Kellen, Y. Kishi, J.R. Delanghe, J.P. van Meerbeeck
• Journal: American Journal of Respiratory and Critical Care Medicine
• Published: 2010;181(6):620-5
• Cited by: 77 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Rationale: Soluble mesothelin (SM) is currently the reference serum biomarker of malignant pleural mesothelioma (MPM). Megakaryocyte potentiating factor (MPF), which originates from the same precursor protein, is potentially more sensitive, yet lacks validation.

Objectives: To analyze the diagnostic performance of MPF as an MPM biomarker and compare this performance with SM.

Methods: A total of 507 participants were enrolled in six cohorts: healthy control subjects (n = 101), healthy asbestos-exposed individuals (n = 89), and patients with benign asbestos-related disease (n = 123), benign respiratory disease (n = 46), lung cancer (n = 63), and MPM (n = 85). Sera were analyzed for SM and MPF levels using the Mesomark and Human MPF ELISA kit, respectively.

Measurements And Main Results: SM and MPF levels differed significantly between patients with MPM and participants from each other cohort (P < 0.001). Receiver operating characteristics curve analysis did not reveal a significant difference between both markers in area under curve (AUC) for distinguishing MPM from all cohorts jointly (SM = 0.871, MPF = 0.849; P = 0.28). At 95% specificity, SM and MPF had a sensitivity of 64% (cutoff = 2.00 nmol/L) and 68% (cutoff = 12.38 ng/ml), respectively. Combining both markers did not improve the diagnostic performance.

Conclusions: In this prospective multicenter study, MPF is validated as a highly performant MPM biomarker. The similar AUC values of SM and MPF, together with the limited difference in sensitivity, show that both serum biomarkers have an equivalent diagnostic performance.

In plain English

This prospective Belgian multicenter study compared two blood markers for malignant pleural mesothelioma: soluble mesothelin (SM, Mesomark kit) and megakaryocyte potentiating factor (MPF). Blood came from 507 people: 101 healthy controls, 89 healthy asbestos-exposed people, 123 patients with benign asbestos-related disease, 46 with benign respiratory disease, 63 with lung cancer and 85 with pleural mesothelioma. Both markers were significantly higher in mesothelioma patients than every other group. For separating mesothelioma from all other groups combined, the area under the curve (a score of how well a test separates groups) was 0.871 (95% confidence interval 0.825 to 0.916) for SM and 0.849 (0.792 to 0.906) for MPF. This difference was not statistically significant. With cutoffs set so that 95% of people without mesothelioma tested negative, SM detected 64% and MPF 68% of mesothelioma patients. Combining the markers did not improve performance. Levels were lower in stage I disease and sarcomatoid tumors, though only four patients had that subtype and the authors urged caution. Twenty-six mesothelioma patients were negative on both tests. The authors concluded the two markers performed equivalently.

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: Prospective multicenter diagnostic study comparing two serum biomarker tests
• Who was studied: 507 participants recruited in Belgium between June 2004 and October 2009, in six groups. The groups were 101 healthy controls; 89 healthy asbestos-exposed individuals; and 123 patients with benign asbestos-related disease (69 pleural plaques, 39 diffuse pleural thickening, 15 predominately asbestosis). They also included 46 patients with benign respiratory disease, 63 with lung cancer and 85 with malignant pleural mesothelioma. The mesothelioma group was made up of 73 epithelioid, 4 sarcomatoid and 8 biphasic cases, at stage I (16), II (22), III (28) and IV (19).
• Exposure: This study tested blood markers; it did not measure asbestos exposure. The asbestos-exposed groups had documented asbestos exposure, and some were enrolled at two Belgian industrial companies with a history of asbestos use or at the Occupational Diseases Fund. Fiber types and doses were not reported.
• Main results:
  • Both SM and MPF levels differed significantly between mesothelioma patients and each of the other groups.
  • For distinguishing mesothelioma from all other groups jointly, SM had an area under the curve of 0.871 (95% confidence interval 0.825 to 0.916).
  • For the same comparison, MPF had an area under the curve of 0.849 (0.792 to 0.906).
  • The areas under the curve for SM and MPF did not differ significantly (P = 0.28 for all groups jointly).
  • At 95% specificity, for mesothelioma versus all groups, SM had a sensitivity of 64% (cutoff 2.00 nmol/L) and MPF had 68% (cutoff 12.38 ng/ml).
  • MPF had a higher sensitivity than SM at 95% specificity against each comparison group, but the improvement was limited.
  • At its optimal cutoff of 1.89 nmol/L, SM had a sensitivity of 66% and a specificity of 94%.
  • At its optimal cutoff of 13.46 ng/ml, MPF had a sensitivity of 68% and a specificity of 97%.
  • A combined marker had an area under the curve of 0.869 for mesothelioma versus all groups, which was no improvement over either marker alone.
  • Patients with sarcomatoid mesothelioma had significantly lower levels than those with epithelioid or biphasic tumors (shown for SM in the quote; MPF showed the same).
  • Patients with stage I mesothelioma had significantly lower levels than those at stages II, III and IV (shown for SM in the quote; MPF showed the same).
  • MPF picked up 5 of the 31 mesothelioma patients without elevated SM.
  • Of the 26 mesothelioma patients negative for both markers, 35% had stage III or IV disease.
• The authors' conclusion: The authors concluded that they had validated MPF as a mesothelioma biomarker and that SM and MPF have an equivalent diagnostic performance. Because combining the markers did not improve detection, they said further work should focus on patients missed by both markers.
• Limitations the authors state:
  • The number of sarcomatoid mesothelioma patients was small, so results for that subtype should be interpreted with caution.
  • In asbestos-exposed people, the positive predictive value of any diagnostic test is limited because mesothelioma is rare. Longitudinal follow-up studies are still needed to show whether marker levels can identify higher-risk exposed people.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Mesothelioma, Biomarker, Pleural Mesothelioma, Lung Cancer.

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