Oral squamous cell carcinoma (OSCC) remains a major global health burden, often diagnosed at advanced stages, with limited survival improvement. Epigenetic dysregulation, particularly promoter hypermethylation, plays a significant role in OSCC pathogenesis. Previous study by Demokan et al. identified Gamma-Aminobutyric Acid Receptor Beta-2 (GABRB2) as a candidate gene subject to methylation-dependent transcriptional silencing. This study aimed to evaluate the methylation and expression profiles of GABRB2 in OSCC and to explore its potential as a diagnostic biomarker. Tissue and serum samples from 48 OSCC patients and 15 healthy controls were analyzed for GABRB2 promoter methylation via quantitative methylation-specific PCR and for gene expression levels via quantitative real-time PCR. Relationships between methylation, expression levels, clinicopathological parameters, and patient outcomes were statistically assessed. GABRB2 promoter hypermethylation was detected in 14.6% of tumor samples, predominantly in floor of the mouth and buccal tumors. Decreased GABRB2 expression was observed in 52.1% of tumor tissues compared to matched-normal tissues, while 22.9% of tumors exhibited increased expression. Methylation-dependent expression loss was confirmed in 71.4% of methylated tumors. Notably, decreased expression and hypermethylation of GABRB2 were correlated with poor prognosis parameters (p < 0.05). ROC analysis showed moderate discrimination for GABRB2 expression in distinguishing tumor from normal tissues (AUC = 0.635, p = 0.022), while serum-based analysis demonstrated poor diagnostic performance. Survival analysis revealed no statistically significant prognostic impact of GABRB2 expression levels (p > 0.05). However, alcohol consumption (p = 0.006) and recurrence developed (p = 0.030) as independent predictors of poor prognosis in multivariate analysis. Our study suggests that there was association between methylation-based expression loss of GABRB2 with OSCC’ subgroups. To our knowledge, this is the first study to investigate GABRB2 gene methylation and expression profiling in both invasive/non-invasive samples from OSCC patients. Hypermethylation in the newly identified candidate GABRB2 gene may play a role in the development of tumors originating from the mouth floor and buccal anatomical regions of the oral cavity. However, since the loss of expression seen in the majority of our patients, we thought that only methylation may not the inhibition mechanism for GABRB2 gene decreased expression. The new identified candidate gene may be specific for the OSCC’s subgroups.
(1) Background: This study investigated the presence of human papillomavirus (HPV), HPV genotypes, Epstein–Barr virus (EBV), cytomegalovirus (CMV) and herpes simplex virus (HSV) in patients with Head and Neck Cancer (HNC) at both molecular and serological levels. (2) Methods Fifty patients with histopathologically confirmed HNC who were admitted to the Department of Otorhinolaryngology, Istanbul Faculty of Medicine. Viral DNA was detected using quantitative real-time PCR, and serological IgM and IgG antibodies were analyzed using the CMIA method; (3) Results: In blood samples, CMV and HSV DNA were not detected, whereas EBV DNA was identified in 2% and HPV DNA in 4% of patients. In tumor tissues, CMV DNA was detected in 8%, EBV DNA in 10%, and HPV DNA in 6%; HSV DNA is 6%. HPV genotypes 18, 45, and 69 were found in tissue samples. Serologically, IgG positivity for CMV, EBV, and HSV-1 exceeded 90%, whereas IgM positivity was low and not statistically significant; (4) Conclusions: HPV, EBV, and CMV DNA were detected at low frequencies in patients with HNC, while HSV DNA was absent. These findings underline the need for larger multi-center studies and support the consideration of routine viral screening, particularly for HPV, in specific tumor subtypes.
Background/Objectives: Recent meta-analyses have established that factors such as sarcopenia, male sex, and low serum albumin significantly correlate with increased postoperative complications in head and neck surgery, with routine neck computed tomography (CT) at the third cervical vertebra (C3) serving as a practical tool for muscle mass assessment. This study aimed to confirm the prognostic value of C3-based sarcopenia and specific clinical comorbidities in predicting early postoperative complications in patients with oral squamous cell carcinoma (OSCC). Methods: A retrospective cohort study was conducted on 167 patients undergoing primary surgery for OSCC. Sarcopenia was assessed using the C3-vertebra skeletal muscle index (SMI) derived from routine preoperative neck CT scans. Clinical and surgical variables, including preoperative serum albumin levels, comorbidities, and flap reconstruction types, were evaluated. A priori multivariate logistic regression models were utilized to identify independent predictors of surgical site and pulmonary and total complications (Clavien–Dindo classification) within 30 days. Results: The overall complication rate was 51%. Multivariate analysis revealed that sarcopenia (aOR: 3.26; 95% CI: 1.11–9.56), male sex (aOR: 3.48; 95% CI: 1.11–10.85), coronary artery disease (CAD) (aOR: 4.30; 95% CI: 1.21–15.36), and free-flap reconstruction (aOR: 15.06; 95% CI: 2.47–92.01) were robust independent predictors of total complications. Male sex (aOR: 4.17; 95% CI: 1.51–11.58) and preoperative hypoalbuminemia (<3.5 g/dL) (aOR: 3.43; 95% CI: 1.20–9.82) were independent predictors of surgical site complications, while regional flap reconstruction was independently associated with pulmonary complications (aOR: 5.97; 95% CI: 1.38–25.97). Conclusions: Sarcopenia, male sex, CAD, and flap reconstruction type are strong independent predictors of postoperative morbidity in OSCC. These findings advocate for “opportunistic screening” of muscle mass via routine preoperative neck CT, alongside rigorous cardiovascular profiling, to identify high-risk phenotypes for targeted perioperative optimization.
19 September 2023 in Environmental and Molecular Mutagenesis