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Updated: Mar 31, 2026
An Ex vivo Culture System to Study Thyroid Development
Published on: June 6, 2014
CHD4 and NOX4 expression in thyroid tumor tissues
Salma Fenniche1,2,3,4, Mohamed Oukabli5,6, Yassire Oubaddou1
1Laboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 1014, Morocco.
Aim:
Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core NURD remodeling complex ATPase that plays a crucial role as a gene repressor. Its overexpression has been reported in several cancers. In papillary thyroid carcinomas (PTCs), CHD4 is overexpressed and associated with aggressive features of the tumor, such as proliferation, migration, and epithelial-mesenchymal transition (EMT). We previously showed in PTCs that NADPH oxidase NOX4 expression is positively regulated by BRAFV600E mutation, which is the most aggressive alteration in PTCs. In this retrospective study, we wondered whether there is a link between CHD4 and NOX4 protein expression in malignant thyroid tissues.
Methods:
We explored CHD4 protein expression by immunostaining analysis in 86 human thyroid tissues: 44 thyroid tumor tissues [28 classical forms of PTCs (C-PTCs), 13 follicular variants of PTCs (F-PTCs), and three anaplastic thyroid carcinomas (ATCs)] and 42 of their normal adjacent tissues (NATs). The detection of BRAFV600E mutation was performed using Sanger sequencing and digital droplet PCR. Statistical analyses were conducted using GraphPad Prism 8 software. Various tests were used to assess the statistical relevance of different correlations, such as the chi-square test, Fisher's exact test, and the Pearson correlation coefficient. A p-value of less than 0.05 indicates statistical significance.
Results:
The CHD4 protein expression analysis with already published data from our group (BRAFV600E status and NOX4 expression) reveals a highly significant level of CHD4 protein expression in C-PTCs compared to F-PTCs and ATC. Importantly, 70% of C-PTCs-BRAFV600E overexpress CHD4 at the protein level, confirming the positive correlation between the CHD4 expression and BRAFV600E mutation. Furthermore, a high level of CHD4 is associated with the presence of capsular breach and vascular emboli, affirming the involvement of CHD4 in thyroid tumor aggressiveness. Interestingly, we showed for the first time, to our knowledge, a positive correlation between CHD4 and NOX4 protein expression in malignant thyroid tissues.
Conclusions:
The results of this study suggest that CHD4 could be used as a complementary molecular marker to improve the diagnosis and the management of PTCs-BRAFV600E .
Insights
Chromodomain-helicase-DNA-binding protein 4 (CHD4) is overexpressed in aggressive papillary thyroid cancers (PTCs) and correlates with the BRAF V600E mutation. This study found a novel positive link between CHD4 and NOX4 expression in thyroid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a key gene repressor and its overexpression is linked to cancer aggressiveness.
- In papillary thyroid carcinomas (PTCs), CHD4 overexpression correlates with proliferation, migration, and epithelial-mesenchymal transition (EMT).
- The BRAF V600E mutation, common in aggressive PTCs, positively regulates NADPH oxidase NOX4 expression.
Purpose of the Study:
- To investigate the relationship between CHD4 and NOX4 protein expression in malignant thyroid tissues.
- To explore the correlation between CHD4 expression and aggressive tumor features, including BRAF V600E mutation status.
Main Methods:
- Immunostaining analysis of CHD4 protein expression in 86 human thyroid tissues (44 tumor, 42 normal adjacent tissues).
- Detection of BRAF V600E mutation using Sanger sequencing and digital droplet PCR.
- Statistical analyses including chi-square, Fisher's exact test, and Pearson correlation coefficient.
Main Results:
- Significantly higher CHD4 protein expression was observed in classical PTCs (C-PTCs) compared to follicular variants (F-PTCs) and anaplastic thyroid carcinomas (ATCs).
- CHD4 overexpression was found in 70% of C-PTCs with BRAF V600E mutation, confirming a positive correlation.
- High CHD4 levels were associated with capsular breach and vascular emboli, indicating involvement in tumor aggressiveness.
- A novel positive correlation between CHD4 and NOX4 protein expression in malignant thyroid tissues was established.
Conclusions:
- CHD4 protein expression is significantly elevated in aggressive PTCs, particularly those with BRAF V600E mutation.
- CHD4 is linked to adverse prognostic factors such as capsular breach and vascular invasion.
- CHD4 may serve as a valuable complementary molecular marker for diagnosing and managing BRAF V600E-mutated PTCs.
