NPM2 in malignant peritoneal mesothelioma: from basic tumor biology to clinical medicine

Our plain-English summary of NPM2 in malignant peritoneal mesothelioma: from basic tumor biology to clinical medicine, by H.L. Wu, Z.R. Yang, L.J. Yan, et al (World Journal of Surgical Oncology, 2022).

The study

• Authors: H.L. Wu, Z.R. Yang, L.J. Yan, Y.D. Su, R. Ma, Y. Li
• Journal: World Journal of Surgical Oncology
• Published: 2022;20(1):141
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: This review systematically summarizes gene biology features and protein structure of nucleoplasmin2 (NPM2) and the relationship between NPM2 and malignant peritoneal mesothelioma (MPM), in order to explore the molecular pathological mechanism of MPM and explore new therapeutic targets.

Methods: NCBI PubMed database was used for the literature search. NCBI Gene and Protein databases, Ensembl Genome Browser, UniProt, and RCSB PDB database were used for gene and protein review. Three online tools (Consurf, DoGSiteScorer, and ZdockServer), the GEPIA database, and the Cancer Genome Atlas were used to analyze bioinformatics characteristics for NPM2 protein.

Results: The main structural domains of NPM2 protein include the N-terminal core region, acidic region, and motif and disordered region. The N-terminal core region, involved in histone binding, is the most conserved domain in the nucleoplasmin (NPM) family. NPM2 with a large acidic tract in its C-terminal tail (NPM2-A2) is able to bind histones and form large complexes. Bioinformatics results indicated that NPM2 expression was correlated with the pathology of multiple tumors. Among mesothelioma patients, 5-year survival of patients with low-NPM2-expression was significantly higher than that of the high-NPM2-expression patients. NPM2 can facilitate the formation of histone deacetylation. NPM2 may promote histone deacetylation and inhibit the related-gene transcription, thus leading to abnormal proliferation, invasion, and metastasis of MPM.

Conclusion: NPM2 may play a key role in the development and progression of MPM.

© 2022. The Author(s).

In plain English

This article was a review of the NPM2 gene and the protein it makes, and of its possible link to malignant peritoneal mesothelioma, a cancer of the lining of the abdomen. The authors searched PubMed and gene and protein databases, and ran their own computer analyses with online tools and public cancer databases. Drawing partly on earlier studies, they described NPM2 as a 214-amino-acid protein that binds histones (proteins that package DNA), mainly through an acidic region called NPM2-A2. In the GEPIA database, NPM2 expression differed significantly between tumor and normal tissue in several cancers. They used data on 84 patients with pleural mesothelioma (in the chest lining, not the abdomen) from the Cancer Genome Atlas. In that group, 5-year survival was significantly higher for patients with low NPM2 expression than for those with high expression. The text gave no survival figures. Unpublished staining from the authors' group showed NPM2 in peritoneal mesothelioma tissue. The authors suggested NPM2 may promote histone deacetylation and so tumor growth and spread. They said the mechanisms need further research. Asbestos was not discussed.

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: Review of the literature and gene/protein databases, with the authors' own bioinformatics analyses of public databases (GEPIA, the Cancer Genome Atlas) and some unpublished laboratory data
• Who was studied: For the survival analysis: 84 patients with pleural mesothelioma whose data were taken from the Cancer Genome Atlas (TCGA). Other parts of the article covered tumor and normal tissue data for many cancer types in the GEPIA database, and unpublished staining of malignant peritoneal mesothelioma tissue from the authors' group (number of patients not given).
• Exposure: No exposure was studied. The article concerns expression of the NPM2 gene and protein; asbestos and fiber types are not mentioned.
• Main results:
  • The review described the full-length NPM2 protein as having 214 amino acids.
  • Citing an earlier crystal-structure study, the review stated that the acidic region NPM2-A2 plays the main role in NPM2 binding to histones.
  • The DoGSiteScorer online tool predicted 3 binding pockets on NPM2, which the authors said may be potential histone-binding sites.
  • In the GEPIA database, NPM2 expression differed significantly between tumor and normal tissue in multiple tumors. These included cholangiocarcinoma, colon adenocarcinoma, adrenocortical carcinoma, glioblastoma, kidney renal clear cell carcinoma, acute myeloid leukemia, brain low-grade glioma, testicular germ cell tumors and thymoma.
  • The 84 pleural mesothelioma patients from TCGA were split into high and low NPM2 expression groups. 5-year survival was significantly higher in the low-NPM2-expression group. No survival percentages, hazard ratios or p-values are given in the text.
  • In unpublished data from the authors' group, NPM2 staining (immunohistochemistry) was positive in malignant peritoneal mesothelioma patients.
  • In the authors' unpublished animal-model study of malignant peritoneal mesothelioma treated with apatinib, NPM2 expression was reported as significantly downregulated in the apatinib group and the control group.
• The authors' conclusion: The authors concluded that NPM2 may promote histone deacetylation and inhibit transcription of related genes, possibly leading to abnormal growth, invasion and spread of malignant peritoneal mesothelioma, and that NPM2 may be a potential therapeutic target.
• Limitations the authors state:
  • The authors stated that the mechanisms linking NPM2 to malignant peritoneal mesothelioma still need further in-depth research.
  • The authors noted that research on the NPM family has focused mainly on NPM1 and that reports on NPM2 are lacking.

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Pathology, Mesothelioma, Metastasis.

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