N6-methyladenosine RNA modification (m6A) is of prognostic value in HPV-dependent vulvar squamous cell carcinoma.
Biomarker
HPV
N6-methyladenosine RNA modification
Vulvar squamous cell carcinoma
m6A
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
01 Sep 2022
01 Sep 2022
Historique:
received:
04
06
2022
accepted:
16
08
2022
entrez:
1
9
2022
pubmed:
2
9
2022
medline:
8
9
2022
Statut:
epublish
Résumé
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. 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. 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. Our study suggests dysregulated m6A modification in HPV-associated VSCC.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
Our study suggests dysregulated m6A modification in HPV-associated VSCC.
Identifiants
pubmed: 36050747
doi: 10.1186/s12885-022-10010-x
pii: 10.1186/s12885-022-10010-x
pmc: PMC9434921
doi:
Substances chimiques
RNA
63231-63-0
N-methyladenosine
CLE6G00625
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
EC 1.14.11.33
FTO protein, human
EC 1.14.11.33
Methyltransferases
EC 2.1.1.-
METTL3 protein, human
EC 2.1.1.62
Adenosine
K72T3FS567
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
943Subventions
Organisme : BONFOR
ID : 2020-2A-12
Organisme : BONFOR
ID : 2021-1A-14
Informations de copyright
© 2022. The Author(s).
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