Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Supic G

PROVIDER: S-EPMC8789922 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundTobacco smoking remains one of the major risk factors for oral cavity cancers (OCC), a subgroup of head and neck cancer (HNC) less attributed to human papillomavirus (HPV) infection. Although a strong dose-dependent association between tobacco smoking and OCC exists, several important questions on the age-dependent effects of this habit remain unanswered. We investigated which life course hypothesis best describes the association between tobacco smoking and HPV-negative (HPV-ve ) OCC in Canada and India.MethodsWe used data from the HeNCe Life study, a hospital-based case-control study conducted in Canada and India, using similar protocols. Cases were newly diagnosed subjects with primary squamous cell carcinomas of the head and neck region. Control subjects were patients with non-cancer selected from various outpatient clinics in a hospital located in the same catchment area as the cases and frequency-matched to cases according to age and sex. We collected information on an array of life course exposures using a structured questionnaire with the help of a life grid. Tobacco exposure (pack-years) during three life periods (≤ 30, 31-50, and >50 years of age) was calculated from the entire life course history of smoking. We used CDx brushes to collect oral exfoliated cells. Alpha HPV DNA detection and genotyping were performed for 36 HPV genotypes using the linear array. Participants who tested positive for HPV were excluded from the analysis. We used the Bayesian relevant life course exposure model (BRLM) to identify the life course hypothesis that best described the relationship between tobacco smoking and HPV-ve OCC.ResultsWe show evidence for a late-life sensitive period (>50 years of age) for tobacco smoking in relation to the risk of HPV-ve OCC in both Canada and India. An increase of 1 pack-year of tobacco smoking increased the risk of OCC by ~3% in both countries.ConclusionOur findings from the Canadian and Indian data suggest that smoking tobacco after 50 years of age may carry a higher risk of developing oral cancer than earlier in life. Further studies are warranted to confirm the results.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets