Diagnostic value of combination of biomarkers for malignant pleural mesothelioma: a systematic review and meta-analysis

Our plain-English summary of Diagnostic value of combination of biomarkers for malignant pleural mesothelioma: a systematic review and meta-analysis, by M. Zhu, Z. Lu, H. Guo, et al (Frontiers in Oncology, 2023).

The study

• Authors: M. Zhu, Z. Lu, H. Guo, X. Gu, D. Wei, Z. Zhang
• Journal: Frontiers in Oncology
• Published: 2023;13:1136049
• Type of article: Systematic review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Early-stage accurate diagnosis of malignant pleural mesothelioma (MPM) has always been a formidable challenge. DNA and protein as biomarkers for the diagnosis of MPM have received considerable attention, and yet the outcomes are inconsistent.

Methods: In this study, a systematic search employing PubMed, EMBASE, and Cochrane Library to identify relevant studies from the first day of databases to October 2021. Moreover, we adopt the QUADAS-2 to evaluate the quality of eligible studies and Stata 15.0 and Review Manager 5.4 software programs to perform the meta-analysis. Additionally, bioinformatics analysis was performed at GEPIA for the purpose of exploring relationship between related genes and the survival time of MPM patients.

Results: We included 15 studies at the DNA level and 31studies at the protein level in this meta-analysis. All results demonstrated that the diagnostic accuracy of the combination of MTAP + Fibulin-3 was the highest with the SEN 0.81 (95% CI: 0.67, 0.89) and the SPE 0.95 (95% CI: 0.90, 0.97). And the bioinformatics analysis indicated that the higher MTAP gene expression level was beneficial to enhance the survival time of MPM patients.

Discussion: Nonetheless, as a result of the limitations of the included samples, it may be necessary to conduct additional research before drawing conclusions.

Systematic Review Registration: https://inplasy.com/inplasy-2022-10-0043/, identifier INPLASY2022100043.

Copyright © 2023 Zhu, Lu, Guo, Gu, Wei and Zhang.

In plain English

This article was a systematic review and meta-analysis of studies testing biomarkers for diagnosing malignant pleural mesothelioma. It did not study asbestos exposure. The authors searched PubMed, Embase and the Cochrane Library up to October 2021. They included 15 studies of the markers BAP1 and MTAP, covering 1054 patients with malignant pleural mesothelioma and 810 without it, along with 31 studies of protein markers. They analysed BAP1 and MTAP alone and combined with mesothelin, SMRP and Fibulin-3. MTAP plus Fibulin-3 had the highest reported accuracy, with pooled sensitivity 0.81 (95% CI 0.67 to 0.89) and specificity 0.95 (95% CI 0.90 to 0.97). BAP1 alone had pooled sensitivity 0.55 (95% CI 0.44 to 0.66) and MTAP alone 0.64 (95% CI 0.54 to 0.73). In public gene data from 86 mesothelioma tumors, higher MTAP expression was associated with longer survival (p = 0.00017). BAP1 expression was not significantly linked to survival. The authors concluded that increasing MTAP expression could prolong survival. They noted the small number of studies, that most were cross-sectional studies of advanced disease, and possibly inconsistent laboratory methods.

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: Systematic review and meta-analysis of diagnostic accuracy studies, plus a bioinformatics survival analysis of public gene-expression data (GEPIA)
• Who was studied: 15 studies at the DNA level (BAP1, MTAP) with 1054 malignant pleural mesothelioma patients and 810 non-MPM patients, plus 31 protein-level studies, found by searching PubMed, Embase and Cochrane up to October 2021. The survival analysis used RNA-seq data from 86 mesothelioma tumor tissues in GEPIA.
• Exposure: No asbestos exposure was studied. The study examined the diagnostic biomarkers BAP1 and MTAP, alone and combined with each other and with mesothelin (MSLN), soluble mesothelin-related peptide (SMRP) and Fibulin-3.
• Main results:
  • The combination MTAP + Fibulin-3 had the highest diagnostic accuracy for malignant pleural mesothelioma: pooled sensitivity 0.81 (95% CI 0.67 to 0.89) and pooled specificity 0.95 (95% CI 0.90 to 0.97).
  • For MTAP + Fibulin-3, the area under the curve was 0.96 (95% CI 0.94 to 0.97).
  • BAP1 alone had a pooled sensitivity of 0.55 (95% CI 0.44 to 0.66).
  • MTAP alone had a pooled sensitivity of 0.64 (95% CI 0.54 to 0.73).
  • In the GEPIA mesothelioma data, survival differed between the high and low MTAP expression groups (p = 0.00017), and higher MTAP expression was associated with longer survival.
  • BAP1 gene expression was not significantly associated with prognosis.
  • The authors reported no publication bias on Deek's funnel plot testing.
• The authors' conclusion: The authors concluded that increasing MTAP gene expression could improve prognosis and prolong survival in malignant pleural mesothelioma patients. This conclusion is based on an association found in gene-expression data.
• Limitations the authors state:
  • The small number of included studies might compromise the reliability of the pooled estimates.
  • Most included studies did not report the time between the diagnostic test and the reference standard test.
  • Most included studies were cross-sectional studies of patients with advanced disease, and laboratory methods may have been inconsistent.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Systematic Review, Meta-Analysis, MTAP, Fibulin-3.

Related studies

• Systematic Review, Meta-Analysis and Bioinformatic Analysis of Biomarkers for Prognosis of Malignant Pleural Mesothelioma — Z. Lu, W. Zhang, et al. (2022)
• Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis — L. Micolucci, M.M. Akhtar, et al. (2016)
• Diagnostic value of fibulin-3 for malignant pleural mesothelioma: A systematic review and meta-analysis — R. Ren, P. Yin, et al. (2016)
• Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: a systematic review and meta-analysis — E. Schillebeeckx, J.P. van Meerbeeck, et al. (2021)
• Prognostic value of maximum standard uptake value, metabolic tumour volume, and total lesion glycolysis of 18F-FDG PET/CT in patients with malignant pleural mesothelioma: a systematic review and meta-analysis — W. Wen, D. Xu, et al. (2022)
• Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis — A. Cui, X.G. Jin, et al. (2014)

Browse more research in Frontiers in Oncology, or return to medical research.