Serum diagnostic markers for malignant pleural mesothelioma: a narrative review

Our plain-English summary of Serum diagnostic markers for malignant pleural mesothelioma: a narrative review, by J.J. Wang, L. Yan (Translational Cancer Research, 2022).

The study

• Authors: J.J. Wang, L. Yan
• Journal: Translational Cancer Research
• Published: 2022;11(12):4434-4440
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background And Objective: The prognosis of patients with malignant pleural mesothelioma (MPM) is poor, and early diagnosis is key to improving the prognosis. Pleural biopsy is the gold reference for diagnosing MPM, but it is an invasive method that can cause operation-related complications such as bleeding and infection. Serum biomarkers, with the advantages of mini-invasiveness, short turnaround time and objectiveness, represent a promising diagnostic tool for MPM.

Methods: We searched the PubMed database to identify clinical studies published between 1990 to July 2022 that investigated the diagnostic accuracy of serum biomarkers for MPM. The major findings of the verified studies were summarized.

Key Content And Findings: Currently, there are many available serum markers for MPM, including mesothelin, soluble mesothelin-related peptides, osteopontin, fibulin-3, high mobility group box 1, and microRNA. Systematic review and meta-analysis evidence indicates that the sensitivity and specificity of these serum markers are less than 0.90. In addition, a large portion of previous studies have limitations, especially the representativeness of the study cohort.

Conclusions: The diagnostic accuracy of currently available serum biomarkers is unsatisfactory, and further studies are needed to investigate novel serum biomarkers.

2022 Translational Cancer Research. All rights reserved.

In plain English

This article was a narrative review, not a new study. The authors searched PubMed for English-language clinical studies, published from 1990 to July 2022, on how accurately blood tests diagnose malignant pleural mesothelioma. They summarized the main findings, especially those of systematic reviews and meta-analyses. They covered mesothelin and soluble mesothelin-related peptides (SMRP), osteopontin, fibulin-3, high mobility group box 1 (HMGB1) and microRNAs. Among the work they reviewed, a 2010 meta-analysis reported an overall sensitivity of 64% and specificity of 89% for SMRP. A meta-analysis reported 65% and 81% for osteopontin. A 2016 systematic review reported 87% and 89% for blood fibulin-3. An early fibulin-3 study of 507 patients reported very high accuracy, but later studies from other centers did not reproduce it. The authors noted that many earlier studies had weaknesses, such as small samples, case-control designs and study groups that were not representative. The authors concluded that current serum markers have only moderate or poor diagnostic accuracy and cannot meet clinical needs, and that new markers need further study.

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 of published diagnostic accuracy studies and of systematic reviews and meta-analyses; no new patient data
• Who was studied: Published English-language diagnostic test accuracy studies, systematic reviews and meta-analyses on serum biomarkers for malignant pleural mesothelioma, found in PubMed for 1 January 1990 to 1 July 2022. The number of studies reviewed is not stated.
• Exposure: Blood (serum or plasma) diagnostic markers: mesothelin, soluble mesothelin-related peptides, osteopontin, fibulin-3, HMGB1, microRNAs and others. Asbestos exposure is discussed only as a risk factor and as a basis for choosing control groups; no fiber type is named.
• Main results:
  • As reported in the review: a 2010 systematic review and meta-analysis found SMRP had an overall sensitivity of 64% and specificity of 89% for MPM.
  • As reported in the review: in an individual patient data meta-analysis, when patients with asbestos exposure were used as the control group, SMRP had an area under the curve (AUC) of 0.80.
  • As reported in the review: a systematic review and meta-analysis found osteopontin had a sensitivity of 65% and specificity of 81%.
  • As reported in the review: an updated meta-analysis gave an AUC of 0.66 for serum osteopontin and 0.69 for plasma osteopontin.
  • As reported in the review: a 2012 study of 507 patients in three cohorts (Detroit, Toronto, New York), all including patients with a history of asbestos exposure, found plasma fibulin-3 sensitivity and specificity above 0.95.
  • As reported in the review: later studies from other centers did not reproduce the fibulin-3 findings. One study found an AUC of only 0.61 for plasma fibulin-3.
  • As reported in the review: a 2016 systematic review found blood fibulin-3 had a sensitivity of 87% and specificity of 89% for MPM.
  • As reported in the review: in a study of 497 people, with patients with asbestosis as the control group, serum HMGB1 had an AUC of 0.56 for diagnosing MPM.
  • As reported in the review: a meta-analysis found circulating miR-126 had an overall sensitivity of 0.71 and specificity of 0.69 for MPM.
  • The Mesomark kit is the only ELISA kit approved by the US FDA for diagnosing MPM.
• The authors' conclusion: The authors concluded that the most widely studied markers (mesothelin, SMRP, osteopontin, fibulin-3) have only moderate or poor diagnostic accuracy, cannot meet clinical needs, and that further studies of new markers are needed.
• Limitations the authors state:
  • Limitation of the studies reviewed, as stated by the authors: many earlier studies had limitations, especially in how representative the study groups were.
  • Limitation of the studies reviewed: most microRNA studies had small samples and design flaws such as case-control designs.
  • Limitation of the studies reviewed: the meta-analysis comparing fibulin-3 with mesothelin used different populations for each marker, so the authors judged the comparison unreliable.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Pleural Biopsy, Biomarker, Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Osteopontin, Fibulin-3.

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