A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors
The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF<sup>V600E</sup> tumors compared to PTC-BRAF<sup>wt</sup> tumors. How...
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MDPI AG
2023-07-01
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author | Salma Fenniche Mohamed Oukabli Yassire Oubaddou Hafsa Chahdi Amal Damiri Abir Alghuzlan Abdelilah Laraqui Nadia Dakka Youssef Bakri Corinne Dupuy Rabii Ameziane El Hassani |
author_facet | Salma Fenniche Mohamed Oukabli Yassire Oubaddou Hafsa Chahdi Amal Damiri Abir Alghuzlan Abdelilah Laraqui Nadia Dakka Youssef Bakri Corinne Dupuy Rabii Ameziane El Hassani |
author_sort | Salma Fenniche |
collection | DOAJ |
description | The comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF<sup>V600E</sup> tumors compared to PTC-BRAF<sup>wt</sup> tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves’ disease, ten goiters, and 20 hyperplasias). We detected the BRAF<sup>V600E</sup> mutation by Sanger sequencing and digital droplet PCR. The results show that NOX4 was found to be higher (score ≥ 2) in C-PTC (92.9%) compared to F-PTC (52.9%) and ATC (33.3%) concerning malignant tumors. Interestingly, all C-PTC-BRAF<sup>V600E</sup> expressed a high score for NOX4 at the protein level, strengthening the positive correlation between the BRAF<sup>V600E</sup> mutation and NOX4 expression. In addition, independent of the mutational status of BRAF, we observed that 90% of C-PTC infiltrating tumors showed high NOX4 expression, suggesting that NOX4 may be considered a complementary biomarker in PTC aggressiveness. Interestingly, NOX4 was highly expressed in non-malignant thyroid diseases with different subcellular localizations. |
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spelling | doaj.art-67e799913472480c8d8fd00253dcfa182023-11-18T18:51:15ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-07-014575811582310.3390/cimb45070367A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid TumorsSalma Fenniche0Mohamed Oukabli1Yassire Oubaddou2Hafsa Chahdi3Amal Damiri4Abir Alghuzlan5Abdelilah Laraqui6Nadia Dakka7Youssef Bakri8Corinne Dupuy9Rabii Ameziane El Hassani10Laboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 1014, MoroccoService of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Rabat 1014, MoroccoLaboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 1014, MoroccoService of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Rabat 1014, MoroccoService of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Rabat 1014, MoroccoGustave Roussy Cancer Campus, Pavillon de Recherche N°2, F-94805 Villejuif, FranceService of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Rabat 1014, MoroccoLaboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 1014, MoroccoLaboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 1014, MoroccoGustave Roussy Cancer Campus, Pavillon de Recherche N°2, F-94805 Villejuif, FranceLaboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 1014, MoroccoThe comparative analysis of the expression of the reactive oxygen species-generating NADPH oxidase NOX4 from TCGA data shows that the NOX4 transcript is upregulated in papillary thyroid carcinomas (PTC)-BRAF<sup>V600E</sup> tumors compared to PTC-BRAF<sup>wt</sup> tumors. However, a comparative analysis of NOX4 at the protein level in malignant and non-malignant tumors is missing. We explored NOX4 protein expression by immunohistochemistry staining in malignant tumors (28 classical forms of PTC (C-PTC), 17 follicular variants of PTC (F-PTC), and three anaplastic thyroid carcinomas (ATCs)) and in non-malignant tumors (six lymphocytic thyroiditis, four Graves’ disease, ten goiters, and 20 hyperplasias). We detected the BRAF<sup>V600E</sup> mutation by Sanger sequencing and digital droplet PCR. The results show that NOX4 was found to be higher (score ≥ 2) in C-PTC (92.9%) compared to F-PTC (52.9%) and ATC (33.3%) concerning malignant tumors. Interestingly, all C-PTC-BRAF<sup>V600E</sup> expressed a high score for NOX4 at the protein level, strengthening the positive correlation between the BRAF<sup>V600E</sup> mutation and NOX4 expression. In addition, independent of the mutational status of BRAF, we observed that 90% of C-PTC infiltrating tumors showed high NOX4 expression, suggesting that NOX4 may be considered a complementary biomarker in PTC aggressiveness. Interestingly, NOX4 was highly expressed in non-malignant thyroid diseases with different subcellular localizations.https://www.mdpi.com/1467-3045/45/7/367papillary thyroid carcinomasBRAF<sup>V600E</sup> hot spot mutationNADPH oxidase NOX4biomarker |
spellingShingle | Salma Fenniche Mohamed Oukabli Yassire Oubaddou Hafsa Chahdi Amal Damiri Abir Alghuzlan Abdelilah Laraqui Nadia Dakka Youssef Bakri Corinne Dupuy Rabii Ameziane El Hassani A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors Current Issues in Molecular Biology papillary thyroid carcinomas BRAF<sup>V600E</sup> hot spot mutation NADPH oxidase NOX4 biomarker |
title | A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors |
title_full | A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors |
title_fullStr | A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors |
title_full_unstemmed | A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors |
title_short | A Comparative Analysis of NOX4 Protein Expression in Malignant and Non-Malignant Thyroid Tumors |
title_sort | comparative analysis of nox4 protein expression in malignant and non malignant thyroid tumors |
topic | papillary thyroid carcinomas BRAF<sup>V600E</sup> hot spot mutation NADPH oxidase NOX4 biomarker |
url | https://www.mdpi.com/1467-3045/45/7/367 |
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