Identification of CD24 as a potential diagnostic and therapeutic target for malignant pleural mesothelioma

Our plain-English summary of Identification of CD24 as a potential diagnostic and therapeutic target for malignant pleural mesothelioma, by S. Karnan, A. Ota, H. Murakami, et al (Cell Death Discovery, 2020).

The study

• Authors: S. Karnan, A. Ota, H. Murakami, M.L. Rahman, M.N. Hasan, M. Wahiduzzaman, I. Hanamura, L. Quang Vu, A. Inoko, T. Hyodo, H. Konishi, S. Tsuzuki, Y. Hosokawa
• Journal: Cell Death Discovery
• Published: 2020;6(1):127
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleura that is currently incurable due to the lack of an effective early diagnostic method and specific medication. The CDKN2A (p16) and NF2 genes are both frequently mutated in MPM. To understand how these mutations contribute to MPM tumor growth, we generated NF2/p16 double-knockout (DKO) cell clones using human MeT-5A and HOMC-B1 mesothelial cell lines. Cell growth and migration activities were significantly increased in DKO compared with parental cells. cDNA microarray analysis revealed differences in global gene expression profiles between DKO and parental cells. Quantitative PCR and western blot analyses showed upregulation of CD24 concomitant with increased phosphorylation of AKT, p70S6K, and c-Jun in DKO clones. This upregulation was abrogated by exogenous expression of NF2 and p16. CD24 knockdown in DKO cells significantly decreased TGF-β1 expression and increased expression of E-cadherin, an epithelial-mesenchymal transition marker. CD24 was highly expressed in human mesothelioma tissues (28/45 cases, 62%) and associated with the loss of NF2 and p16. Public data analysis revealed a significantly shorter survival time in MPM patients with high CD24 gene expression levels. These results strongly indicate the potential use of CD24 as a prognostic marker as well as a novel diagnostic and therapeutic target for MPM.

In plain English

This was a laboratory study. The authors used the CRISPR/Cas9 system to knock out the NF2 and CDKN2A (p16) genes, singly and together (double knockout, DKO), in two immortalized human mesothelial cell lines, MeT-5A and HOMC-B1. Cell growth, soft-agar colony formation and migration were significantly increased in the DKO clones compared with the parental cells. Microarray and follow-up testing showed higher CD24 expression in DKO clones, together with increased phosphorylation of AKT, p70S6K and c-Jun; putting NF2 and p16 back into the cells reduced these increases. Knocking down CD24 reduced cell growth, lowered TGF-beta1, Snail and N-cadherin, and raised E-cadherin. In tissue arrays of 45 mesothelioma samples, staining was scored strong (3+) in 8, moderate (2+) in 20 and weak (1+) in 6, with no staining in 3 normal mesothelium samples. In public TCGA data on 86 patients, higher CD24 expression accompanied shorter overall survival. The authors concluded CD24 may serve as a prognostic marker and a diagnostic and therapeutic target for malignant pleural mesothelioma.

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: Laboratory cell-line experiment (CRISPR/Cas9 gene knockout) with immunohistochemistry on human tissue arrays and analysis of a public gene-expression/survival dataset
• Who was studied: Human mesothelial cell lines MeT-5A and HOMC-B1 (and mesothelioma line Y-MESO-9); a purchased tissue array of 45 mesothelioma cases and 3 normal mesothelium samples; and a public cohort of 86 patients from The Cancer Genome Atlas Mesothelioma. Work done at Aichi Medical University, Japan
• Exposure: No asbestos or other human exposure was measured; the experimental manipulation was CRISPR/Cas9 knockout of the NF2 and CDKN2A (p16) genes, re-expression of NF2 and p16, shRNA knockdown of CD24, and treatment with the TGF-beta1 inhibitor vactosertib. Asbestos is mentioned only as background in the introduction
• Main results:
  • In the cell lines, growth, colony formation and migration were higher in NF2/p16 double-knockout clones than in parental cells
  • CD24 (and PTN, BMP7, CADM1) expression rose in DKO clones and fell again when NF2 and p16 were re-expressed
  • Knocking down CD24 in DKO cells reduced growth and shifted EMT-related markers
  • Staining of the 45 mesothelioma tissue samples: 8 strong (3+), 20 moderate (2+), 6 weak (1+); the 3 normal mesothelium samples were negative
  • In the public TCGA cohort of 86 patients, split at a log2 CD24 value of 6.938 into high (n = 42) and low (n = 44), high CD24 expression was associated with shorter overall survival (P < 0.0001)
  • In tissue arrays, CD24 positivity was seen in 20 (100%) of 20 cases negative for both NF2 and p16, versus 8 (42%) of 19 cases positive for both
• The authors' conclusion: The authors concluded that CD24 is commonly expressed in mesothelioma tissue and associated with poor prognosis, and may therefore be used as a prognostic marker and as a diagnostic and therapeutic target for MPM, with further study needed
• Limitations the authors state:
  • The authors state that the mechanism by which loss of NF2 and p16 raises CD24 expression is not known
  • The authors note mismatches between mRNA and protein expression patterns for CADM1, PTN and BMP7, which they attribute in part to post-transcriptional modification

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleura, CDKN2A, Mesothelial Cells, Mesothelioma.

Related studies

• CAMK2D: a novel molecular target for BAP1-deficient malignant mesothelioma — S. Karnan, A. Ota, et al. (2023)
• Identification of pregnancy-associated plasma protein A as a migration-promoting gene in malignant pleural mesothelioma cells: a potential therapeutic target — J. Huang, S. Tabata, et al. (2013)
• Development and Evaluation of Antibody Proteomics Technology for Rapid and Comprehensive Identification of Potential Biomarkers and Therapeutic Targets — K. Nagano (2018)
• Identification of Novel Biomarkers and Potential Therapeutic Targets for Systemic Sclerosis: An Integrated Analysis of Plasma Proteome-Wide Mendelian Randomization and Transcriptome — H. Li, Q. Li, et al. (2025)
• Targeting fatty acid synthase suppresses tumor development in NF2/CDKN2A-deficient pleural mesothelioma — S. Karnan, A. Ota, et al. (2026)
• The "don't eat me" signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma — C.M. Schürch, S. Forster, et al. (2017)

Browse more research in Cell Death Discovery, or return to medical research.