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N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma
BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is an uncommon gynecologic malignancy but with an increasing incidence in recent years. Etiologically, VSCC is classified into two subtypes: HPV-dependent and HPV-independent. Localized VSCC is treated surgically and/or with radiation therapy, but fo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434921/ https://www.ncbi.nlm.nih.gov/pubmed/36050747 http://dx.doi.org/10.1186/s12885-022-10010-x |
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author | Condic, Mateja Thiesler, Thore Staerk, Christian Klümper, Niklas Ellinger, Jörg Egger, Eva K. Kübler, Kirsten Kristiansen, Glen Mustea, Alexander Ralser, Damian J. |
author_facet | Condic, Mateja Thiesler, Thore Staerk, Christian Klümper, Niklas Ellinger, Jörg Egger, Eva K. Kübler, Kirsten Kristiansen, Glen Mustea, Alexander Ralser, Damian J. |
author_sort | Condic, Mateja |
collection | PubMed |
description | BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is an uncommon gynecologic malignancy but with an increasing incidence in recent years. Etiologically, VSCC is classified into two subtypes: HPV-dependent and HPV-independent. Localized VSCC is treated surgically and/or with radiation therapy, but for advanced, metastatic or recurrent disease, therapeutic options are still limited. N6-methyladenosine (m6A) is the most prevalent post-transcriptional messenger RNA (mRNA) modification and involved in many physiological processes. The group of m6A proteins can be further divided into: ‚writers’ (METTL3, METTL4, METTL14, WTAP, KIAA1429), ‚erasers’ (FTO, ALKBH5), and ‚readers’ (HNRNPA2B1, HNRNPC, YTHDC1, YTHDF1-3). Dysregulated m6A modification is implicated in carcinogenesis, progression, metastatic spread, and drug resistance across various cancer entities. Up to date, however, only little is known regarding the role of m6A in VSCC. METHODS: Here, we comprehensively investigated protein expression levels of a diverse set of m6A writers, readers and erasers by applying immunohistochemical staining in 126 patients with primary VSCC. RESULTS: In the entire study cohort, dominated by HPV-independent tumors, m6A protein expression was not associated with clinical outcome. However, we identified enhanced protein expression levels of the ‚writers’ METTL3, METTL14 and the ‚reader’ YTHDC1 as poor prognostic markers in the 23 patients with HPV-dependent VSCC. CONCLUSION: Our study suggests dysregulated m6A modification in HPV-associated VSCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10010-x. |
format | Online Article Text |
id | pubmed-9434921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-94349212022-09-02 N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma Condic, Mateja Thiesler, Thore Staerk, Christian Klümper, Niklas Ellinger, Jörg Egger, Eva K. Kübler, Kirsten Kristiansen, Glen Mustea, Alexander Ralser, Damian J. BMC Cancer Research BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is an uncommon gynecologic malignancy but with an increasing incidence in recent years. Etiologically, VSCC is classified into two subtypes: HPV-dependent and HPV-independent. Localized VSCC is treated surgically and/or with radiation therapy, but for advanced, metastatic or recurrent disease, therapeutic options are still limited. N6-methyladenosine (m6A) is the most prevalent post-transcriptional messenger RNA (mRNA) modification and involved in many physiological processes. The group of m6A proteins can be further divided into: ‚writers’ (METTL3, METTL4, METTL14, WTAP, KIAA1429), ‚erasers’ (FTO, ALKBH5), and ‚readers’ (HNRNPA2B1, HNRNPC, YTHDC1, YTHDF1-3). Dysregulated m6A modification is implicated in carcinogenesis, progression, metastatic spread, and drug resistance across various cancer entities. Up to date, however, only little is known regarding the role of m6A in VSCC. METHODS: Here, we comprehensively investigated protein expression levels of a diverse set of m6A writers, readers and erasers by applying immunohistochemical staining in 126 patients with primary VSCC. RESULTS: In the entire study cohort, dominated by HPV-independent tumors, m6A protein expression was not associated with clinical outcome. However, we identified enhanced protein expression levels of the ‚writers’ METTL3, METTL14 and the ‚reader’ YTHDC1 as poor prognostic markers in the 23 patients with HPV-dependent VSCC. CONCLUSION: Our study suggests dysregulated m6A modification in HPV-associated VSCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-10010-x. BioMed Central 2022-09-01 /pmc/articles/PMC9434921/ /pubmed/36050747 http://dx.doi.org/10.1186/s12885-022-10010-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Condic, Mateja Thiesler, Thore Staerk, Christian Klümper, Niklas Ellinger, Jörg Egger, Eva K. Kübler, Kirsten Kristiansen, Glen Mustea, Alexander Ralser, Damian J. N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma |
title | N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma |
title_full | N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma |
title_fullStr | N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma |
title_full_unstemmed | N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma |
title_short | N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma |
title_sort | n6-methyladenosine rna modification (m6a) is of prognostic value in hpv-dependent vulvar squamous cell carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434921/ https://www.ncbi.nlm.nih.gov/pubmed/36050747 http://dx.doi.org/10.1186/s12885-022-10010-x |
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