Prognostic impact of miR-34b/c DNA methylation, gene expression, and promoter polymorphism in HPV-negative oral squamous cell carcinomas.
Adult
Aged
Aged, 80 and over
Alphapapillomavirus
/ genetics
Biomarkers, Tumor
/ genetics
Case-Control Studies
DNA Methylation
/ genetics
Female
Follow-Up Studies
Gene Expression
Humans
Male
MicroRNAs
/ genetics
Middle Aged
Mouth Neoplasms
/ genetics
Papillomavirus Infections
/ diagnosis
Polymorphism, Single Nucleotide
Prognosis
Promoter Regions, Genetic
Serbia
/ epidemiology
Squamous Cell Carcinoma of Head and Neck
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 01 2022
25 01 2022
Historique:
received:
02
09
2021
accepted:
03
01
2022
entrez:
26
1
2022
pubmed:
27
1
2022
medline:
5
3
2022
Statut:
epublish
Résumé
Micro RNAs (miRNAs) have a key role in gene expression regulation in cancer. The aim of the current study is to evaluate the prognostic value of miR-34b/c promoter hypermethylation, gene expression, and polymorphism in HPV-negative oral squamous cell carcinomas (OSCC). MiR-34b/c promoter hypermethylation and pre-miR-34b/c polymorphism rs4938723 were evaluated in tumor tissues of 148 patients, and miR-34b expression in 123 HPV-negative OSCC. For risk assessment, the control group was comprised of 175 healthy individuals. MiR-34b/c promoter hypermethylation was determined by methylation-specific PCR. Gene expression, genotyping and HPV screening was assessed by Q-PCR. The data from our hospital cohort indicated that miR-34b/c DNA methylation was associated with nodal status (p = 0.048), and predicted the shorter overall survival of HPV-negative OSCC patients (p = 0.008). Down-regulated miR-34b/c expression was associated with smoking (p = 0.047), alcohol use (p = 0.009), stage (p = 0.025), recurrences (p = 0.000), and a poor survival (p = 0.00029). Median values of miR-34b expression were significantly lower in advanced stages III/IV as opposed to stage I/II, p = 0.006, and in nodal positive vs negative patients (p = 0.045). TCGA data also indicated that tumors with stage I-III expressed significantly higher levels of miR-34b, compared to tumors with stage IV (p = 0.035), Low miR-34b/c expression was associated with poor survival in smokers (p = 0.001) and patients with tongue carcinomas (p = 0.00003), and TCGA analysis confirmed these findings although miR-34b expression and miR-34b/c methylation were not associated with survival outcome in the whole TCGA cohort. A significant negative miR-34b/c expression-methylation correlation was observed in our hospital cohort (p = 0.017) and in TCGA cohort. Pre-miR-34b/c polymorphism was not associated with oral cancer risk. Our findings indicate that miR-34b/c hypermethylation and low miR-34b expression could promote the progression and predict the poor prognosis for HPV-negative OSCC, which suggests miR-34b/c as a promising biomarker and therapeutic target for OSCC in the future.
Identifiants
pubmed: 35079080
doi: 10.1038/s41598-022-05399-1
pii: 10.1038/s41598-022-05399-1
pmc: PMC8789922
doi:
Substances chimiques
Biomarkers, Tumor
0
MIRN34 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1296Subventions
Organisme : Medical Faculty of Military Medical Academy
ID : MFVMA/2/20-22
Informations de copyright
© 2022. The Author(s).
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