A Community-Driven, Openly Accessible Molecular Pathway Integrating Knowledge on Malignant Pleural Mesothelioma

Our plain-English summary of A Community-Driven, Openly Accessible Molecular Pathway Integrating Knowledge on Malignant Pleural Mesothelioma, by M. Martens, F. Kreidl, F. Ehrhart, et al (Frontiers in Oncology, 2022).

The study

• Authors: M. Martens, F. Kreidl, F. Ehrhart, D. Jean, M. Mei, H.M. Mortensen, A. Nash, P. Nymark, C.T. Evelo, F. Cerciello
• Journal: Frontiers in Oncology
• Published: 2022;12:849640
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy mainly triggered by exposure to asbestos and characterized by complex biology. A significant body of knowledge has been generated over the decades by the research community which has improved our understanding of the disease toward prevention, diagnostic opportunities and new treatments. Omics technologies are opening for additional levels of information and hypotheses. Given the growing complexity and technological spread of biological knowledge in MPM, there is an increasing need for an integrating tool that may allow scientists to access the information and analyze data in a simple and interactive way. We envisioned that a platform to capture this widespread and fast-growing body of knowledge in a machine-readable and simple visual format together with tools for automated large-scale data analysis could be an important support for the work of the general scientist in MPM and for the community to share, critically discuss, distribute and eventually advance scientific results. Toward this goal, with the support of experts in the field and informed by existing literature, we have developed the first version of a molecular pathway model of MPM in the biological pathway database WikiPathways. This provides a visual and interactive overview of interactions and connections between the most central genes, proteins and molecular pathways known to be involved or altered in MPM. Currently, 455 unique genes and 247 interactions are included, derived after stringent manual curation of an initial 39 literature references. The pathway model provides a directly employable research tool with links to common databases and repositories for the exploration and the analysis of omics data. The resource is publicly available in the WikiPathways database (Wikipathways : WP5087) and continues to be under development and curation by the community, enabling the scientists in MPM to actively participate in the prioritization of shared biological knowledge.

Copyright © 2022 Martens, Kreidl, Ehrhart, Jean, Mei, Mortensen, Nash, Nymark, Evelo and Cerciello.

In plain English

This article described how the authors built an online, computer-readable map of the molecular pathways involved in malignant pleural mesothelioma (MPM) in the public database WikiPathways (entry WP5087). It did not study patients or asbestos exposure. In July 2021 the authors searched PubMed for papers on MPM genetics and molecular pathways, mainly published after 2015. Papers explicitly exploring asbestos were excluded. From 26 review papers and fifteen research papers, they drew a pathway containing 455 genes or gene products, thirteen pathways, fourteen metabolites and 247 unique interactions. In that literature, BAP1, NF2, LATS2, CDKN2A, TP53 and SETD2 were among the most frequently mutated tumor suppressor genes in MPM, along with mutations in the TERT promoter region. The authors used BAP1 as a worked example of how the map links to other databases. The authors concluded that they had provided an initial, disease-centered pathway model that researchers can edit and use for data analysis. They noted that the search was not a full systematic review and left out the effects of asbestos and non-human studies.

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: Development of an online molecular pathway model (knowledge base resource) based on a literature curation; not a patient or exposure study
• Who was studied: Published papers, not people: a PubMed literature search in July 2021 on malignant pleural mesothelioma genetics and molecular or signaling pathways, mainly papers published after 2015 with human relevance; 26 review papers and fifteen research papers were used
• Exposure: No exposure was studied; papers explicitly exploring asbestos were excluded so that the work focused on MPM biology rather than the processes by which it is caused
• Main results:
  • The MPM pathway model included 455 genes/gene products, thirteen pathways, fourteen metabolites and 247 unique interactions
  • In the curated literature, BAP1, NF2, LATS2, CDKN2A, TP53 and SETD2 were among the most frequently mutated tumor suppressor genes in MPM, together with frequently observed mutations of the TERT promoter region
  • The BAP1 section of the pathway was presented as a user example showing links to gene, protein and mutation databases
  • The pathway was uploaded to WikiPathways and made publicly available
• The authors' conclusion: The authors concluded that they had provided an initial, disease-centered pathway model for biomedical research in MPM that allows large-scale data analysis and lets community scientists take part directly in shaping it
• Limitations the authors state:
  • The literature curation was not a fully comprehensive systematic review. It focused on the most central and well-known mechanisms.
  • Detailed search on the effects of asbestos in causing MPM, and non-human studies, were excluded
  • The literature search was a selected starting point drawn from recent years rather than an exhaustive overview

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma.

Related studies

• Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer — M. Rigon, L. Mutti, et al. (2024)
• Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma — M. Carbone, H. Yang (2012)
• Asbestos, lung cancers, and mesotheliomas: from molecular approaches to targeting tumor survival pathways — N.H. Heintz, Y.M. Janssen-Heininger, et al. (2010)
• Molecular pathways and diagnosis in malignant mesothelioma: A review of the 14th International Conference of the International Mesothelioma Interest Group — D.B. Chapel, A. Churg, et al. (2019)
• Connecting molecular pathways to hereditary cancer risk syndromes — J.R. Testa, D. Malkin, et al. (2013)
• Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights — F. Fortarezza, F. Pezzuto, et al. (2022)

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