Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on

Our plain-English summary of Biomarkers for Early Diagnosis and Prognosis of Malignant Pleural Mesothelioma: The Quest Goes on, by C. Ledda, P. Senia, V. Rapisarda (Cancers, 2018).

The study

• Authors: C. Ledda, P. Senia, V. Rapisarda
• Journal: Cancers
• Published: 2018;10(6)
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MM) is a highly aggressive tumor characterized by a poor prognosis. Although its carcinogenesis mechanism has not been strictly understood, about 80% of MM can be attributed to occupational and/or environmental exposure to asbestos fibers. The identification of non-invasive molecular markers for an early diagnosis of MM has been the subject of several studies aimed at diagnosing the disease at an early stage. The most studied biomarker is mesothelin, characterized by a good specificity, but it has low sensitivity, especially for non-epithelioid MM. Other protein markers are Fibulin-3 and osteopontin which have not, however, showed a superior diagnostic performance. Recently, interesting results have been reported for the HMGB1 protein in a small but limited series. An increase in channel proteins involved in water transport, aquaporins, have been identified as positive prognostic factors in MM, high levels of expression of aquaporins in tumor cells predict an increase in survival. MicroRNAs and protein panels are among the new indicators of interest. None of the markers available today are sufficiently reliable to be used in the surveillance of subjects exposed to asbestos or in the early detection of MM. Our aim is to give a detailed account of biomarkers available for MM.

In plain English

This perspective article, a narrative review by occupational medicine authors in Catania, Italy, reported no new data and examined published research on markers for early detection or prognosis of malignant pleural mesothelioma. It covered mesothelin, osteopontin, fibulin-3, HMGB1, aquaporin-1 and microRNAs. One study found mesothelin had 96% specificity but only 47% sensitivity. A six-study osteopontin meta-analysis reported sensitivity 0.65 (95% CI 0.60 to 0.70) and specificity 0.81 (95% CI 0.78 to 0.85). Fibulin-3 had an AUC of 0.99 in its first study, but 0.87, with sensitivity 0.73, in a separate sample. In another group of 153 patients, 82 with mesothelioma, plasma fibulin-3 at a 52 ng/mL cut-off had 22% sensitivity. One study reported that serum hyperacetylated HMGB1, at a threshold of 2.0 ng/mL, had 100% sensitivity and specificity in distinguishing mesothelioma patients from asbestos-exposed subjects and healthy controls. High aquaporin-1 levels in tumor cells were described as predicting longer survival. The authors concluded that no current marker is suitable for early diagnosis of mesothelioma in asbestos-exposed people. They suggested that combining protein markers and microRNAs could help.

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: Perspective article (narrative review of published studies on mesothelioma biomarkers); no new data collected
• Who was studied: No study population of its own; the authors reviewed published studies of biomarkers in patients with malignant pleural mesothelioma, asbestos-exposed people and healthy controls
• Exposure: Not an exposure study; reviewed biomarkers (mesothelin, osteopontin, fibulin-3, HMGB1, aquaporin-1, microRNAs) considered for early diagnosis and prognosis of malignant pleural mesothelioma in high-risk groups such as people formerly exposed to asbestos
• Main results:
  • Reported from a study by Hollevoet and colleagues (not this review): mesothelin had a specificity of 96% and a sensitivity of 47%
  • Reported from a meta-analysis by Hu and colleagues of six studies: overall sensitivity of circulating osteopontin 0.65 (95% CI 0.60 to 0.70) and specificity 0.81 (95% CI 0.78 to 0.85)
  • Reported from Pass et al. 2012 (92 mesothelioma cases, 290 controls): fibulin-3 AUC 0.99. On validation in an external sample, AUC fell to 0.87 and sensitivity to 0.73
  • Reported from Creaney et al. (153 patients, 82 with mesothelioma): plasma fibulin-3 sensitivity 22% and specificity 95% (cut-off 52 ng/mL, AUC 0.671), lower than mesothelin in the same patients
  • Reported from Napolitano et al.: at a threshold of 2.0 ng/mL, hyperacetylated HMGB1 in serum had 100% sensitivity and specificity for distinguishing mesothelioma patients from asbestos-exposed subjects and healthy controls
  • Reported from cited studies: high aquaporin-1 expression in mesothelioma tumor cells predicted longer survival
  • Reported from a meta-analysis by Tian and colleagues of eight studies involving 579 patients: soluble mesothelin level was significantly correlated with survival (pooled HR 1.958, 95% CI 1.531 to 2.504)
• The authors' conclusion: The authors concluded that none of the currently available markers is suitable for early diagnosis of mesothelioma in people exposed to asbestos. They suggested that combining several protein markers and microRNAs might improve diagnostic accuracy, but noted that moving these results into clinical practice remains problematic
• Limitations the authors state:
  • Limitation of the reviewed osteopontin studies, as stated by the authors: different assays were used and control groups were not always appropriate
  • Limitation of the reviewed mesothelin prognosis studies, as stated by the authors: small samples and differing treatments
  • The authors noted that moving research results into clinical practice remains problematic

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Prognosis, Pleural Mesothelioma, Carcinogenesis, Environmental Exposure, Mesothelin, Non-epithelioid, Fibulin-3.

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