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Prognostic impact of miR-34b/c DNA methylation, gene expression, and promoter polymorphism in HPV-negative oral squamous cell carcinomas

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 hypermethyl...

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Hauptverfasser: Supic, Gordana (VerfasserIn) , Stefik, Debora (VerfasserIn) , Ivkovic, Nemanja (VerfasserIn) , Šami, Ahmad (VerfasserIn) , Zeljic, Katarina (VerfasserIn) , Jovic, Sasa (VerfasserIn) , Kozomara, Ruzica (VerfasserIn) , Vojvodic, Danilo (VerfasserIn) , Stosic, Srboljub (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 25 January 2022
In: Scientific reports
Year: 2022, Jahrgang: 12, Pages: 1-13
ISSN:2045-2322
DOI:10.1038/s41598-022-05399-1
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41598-022-05399-1
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-022-05399-1
Volltext
Verfasserangaben:Gordana Supic, Debora Stefik, Nemanja Ivkovic, Ahmad Sami, Katarina Zeljic, Sasa Jovic, Ruzica Kozomara, Danilo Vojvodic & Srboljub Stosic
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Zusammenfassung: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.
Beschreibung:Gesehen am 27.06.2023
Beschreibung:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-022-05399-1

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