Biomarkers in mesothelioma

Our plain-English summary of Biomarkers in mesothelioma, by D.T. Arnold, N.A. Maskell (Annals of Clinical Biochemistry, 2018).

The study

• Authors: D.T. Arnold, N.A. Maskell
• Journal: Annals of Clinical Biochemistry
• Published: 2018;55(1):49-58
• Type of article: Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma is an aggressive cancer of pleural and peritoneal cells that is difficult to diagnose and monitor. Numerous studies have attempted to identify a blood- or pleural fluid-based biomarker that could be used in the diagnostic pathway. More recently, there has been interest in the ability of serum/plasma biomarkers to monitor mesothelioma, given the development of newer treatments and limitations of radiological assessment. The majority of research has focused on soluble mesothelin, a soluble glycoprotein expressed by mesothelial cells. Although soluble mesothelin lacks the sensitivity to be used as a standalone diagnostic marker, serial measurements may be informative, with rising concentrations indicating disease progression and poor survival. High concentrations of other soluble glycoproteins, such as osteopontin, fibulin-3 and vascular endothelial growth factor are independently associated with poor prognosis at baseline, although further research is required to ascertain any role outside of clinical trials. More recent literature has focused on the development of novel biomarkers from discovery cohorts. Although many DNA and mRNA biomarkers show promise in the diagnosis or screening of mesothelioma, none have been prospectively evaluated for use in clinical practice. In this review article, we highlight the potential utility of biomarkers and evaluate the existing literature.

In plain English

This article was a review of published research on blood and pleural fluid biomarkers for mesothelioma, not a new study. A 2014 meta-analysis of 28 studies of serum soluble mesothelin found a pooled sensitivity of 0.61 and specificity of 0.87; for pleural fluid mesothelin it found 0.79 and 0.85. Nine studies of repeated mesothelin measurements all found that a fall from baseline correlated with treatment response or improved survival, but the authors noted that many patients, especially with sarcomatoid histology, have low or undetectable levels. A meta-analysis of nine serum and plasma osteopontin studies, with considerable heterogeneity, found a pooled sensitivity of 0.57 (95% CI 0.52 to 0.61) and specificity of 0.81 (95% CI 0.79 to 0.84); several studies linked high baseline plasma osteopontin to poor prognosis. A meta-analysis of eight fibulin-3 studies gave pooled sensitivity of 0.87 (95% CI 0.58 to 0.97) and specificity of 0.89 (95% CI 0.77 to 0.95). The authors concluded that biomarker panels show promise but none has been externally validated in prospective trials, and that serum mesothelin may help monitor disease during treatment.

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: Narrative review article (commissioned review) of published research on biomarkers in mesothelioma
• Who was studied: No patients were studied directly. The authors reviewed published studies that sought blood- or pleural fluid-based biomarkers for diagnosing, screening, predicting prognosis in, and monitoring mesothelioma.
• Exposure: Not an exposure study. The review concerned biomarkers: soluble mesothelin, megakaryocyte potentiating factor, osteopontin, fibulin-3, hyaluronic acid, VEGF, microRNA, proteomic panels and ENOX2. Asbestos exposure is discussed as the main cause of mesothelioma and as defining an at-risk population for screening.
• Main results:
  • The review reported that a 2014 meta-analysis by Cui et al, covering 28 studies of serum soluble mesothelin, gave pooled sensitivity and specificity of 0.61 and 0.87.
  • In the same meta-analysis, pleural fluid mesothelin gave pooled sensitivity and specificity of 0.79 and 0.85, with cut-offs varying from 3.5 to 24.05 nmol/L.
  • The authors' literature review found nine studies of serial mesothelin measurements. All nine found that a falling mesothelin from baseline correlated with treatment response or improved overall survival.
  • The authors noted that many patients, especially those with sarcomatoid histology, have low or undetectable mesothelin levels despite advanced disease.
  • A 2014 meta-analysis of serum and plasma osteopontin (9 studies, with considerable heterogeneity between them) gave pooled sensitivity of 0.57 (95% CI 0.52 to 0.61) and specificity of 0.81 (95% CI 0.79 to 0.84).
  • Several studies cited in the review found that high baseline plasma osteopontin was associated with poor prognosis.
  • For fibulin-3, a first study reported 100% sensitivity and 94.1% specificity for early-stage mesothelioma in an asbestos-exposed population, but follow-up studies did not replicate this. A meta-analysis of eight studies gave pooled sensitivity of 0.87 (95% CI 0.58 to 0.97) and specificity of 0.89 (95% CI 0.77 to 0.95).
  • In a 2013 study by Creaney et al, 96 patients with mesothelioma were followed up. Those with pleural fluid hyaluronic acid above 75 mg/L had better survival (18.0 months) than those with lower levels (12.6 months) (p less than 0.01).
  • In a study of 51 patients with mesothelioma in an asbestos-exposed population, VEGF had sensitivity of 70.6% and specificity of 88.1%, which the authors judged insufficient for a diagnostic pathway.
• The authors' conclusion: The authors concluded that no single biomarker reproducibly distinguishes mesothelioma from other benign or malignant conditions. Biomarker panels show promise but none has undergone external validation in prospective trials. Several studies support serum mesothelin for monitoring during treatment, though its use in non-epithelioid disease is questioned. High baseline plasma osteopontin appears to be an independent indicator of poor prognosis, but further studies are needed.

Topics

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

Medical terms in this study, explained in our Lexicon: Biomarker, Mesothelioma, Mesothelin, Glycoprotein, Mesothelial Cells, Disease Progression, Osteopontin, Fibulin-3.

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