Despite progress in the treatment of head and neck squamous cell carcinoma (HNSCC) in recent decades, including new surgical techniques, radiotherapy advances and chemotherapy schedules, the prognosis for the affected patients has not improved at the same pace, and still, most HNSCC patients are diagnosed in advanced stages. To increase their survival, the development of better screening methods for early detection is required and appropriate tailored therapeutic interventions are desired. The aim of the present study was to evaluate miRNAs as prognostic biomarkers in patients undergoing organ preservation protocol for locally advanced HNSCC. For this purpose, we assessed the global miRNA expression profile of 15 HNSCC patients (‘screening set’) to identify miRNAs differentially expressed in responders and non-responders to therapy. Four miRNAs differentially expressed in HNSCC samples from the ‘screening set’ were validated in a different cohort of patients (47 samples - ‘validation set’). The results from the ‘validation set’ showed that the higher expression of one of these miRNAs, miR-21, was negatively associated with the treatment response to the organ preservation protocol (p=0.029). A multivariate analysis showed that, in a model adjusted for age, tumor site, p16 immunoexpression and tumor resectability, high expression of miR-21 remained an independent predictor of poor response to the organ preservation protocol (OR=5.69; 95%CI 1.27-25.58; p=0.023), together with clinical stage IV (OR=5.05; 95%CI 1.22-20.88; p=0.025). Furthermore, considering the entire cohort, patients with high expression of miR-21 had worse survival. A multivariate Cox regression analysis also showed miR-21 (HR=2.05; 95%CI 1.05-4.02; p=0.036) and clinical stage IV (HR=3.17; 95%CI 1.49-6.77; p=0.003) as independent prognostic factors (model adjusted for age, tumor site, tumor resectability, and sets ‘screening’ or ‘validation’).In conclusion, the results of this study suggest that the evaluation of miR-21 expression could be an important tool for treatment planning and a prognosis predictior for HNSCC patients undergoing organ preservation protocols.

Genome-wide DNA methylation profiling of esophageal squamous cell carcinoma from global high incidence regions identifies crucial genes and potential cancer markers

Background: Head and neck squamous cell carcinoma (HNSCC) is usually associated to tobacco and alcohol consumption. Increased telomerase activity has been consistently detected in 80-90% of malignant tumors, including HNSCC. Mutations within the promoter region of telomerase reverse transcriptase (TERT) that confer enhanced TERT promoter activity have been reported in two major hotspots, designated C228T and C250T. Objectives: To evaluate TERT promoter mutations C228T and C250T in HNSCC patients from Brazil and correlate with patients' outcome. Materials and Methods: Formalin-fixed paraffin-embedded tissues were obtained from 88 HNSCC patients and analyzed for TERT promoter mutations C228T and C250T by pyrosequencing. Results: The overall prevalence of hotspot TERT mutations in HNSCC samples was of 27.3%, with 6.8% at locus C228T and 20.5% at C250T. The majority (92%) of mutated cases were located in oral cavity, mainly at the tongue. We observed that 94.4% of the patients harboring TERT promoter mutation C250T were alcohol consumers (p = 0.032) and 66.7% of the patients harboring TERT promoter mutation C228T were not alcohol consumers (p = 0.035). The presence of C228T mutation impacted patient outcome, with a significant decrease in disease-free survival (20.0 vs. 63.0%, p =0.017) and in overall survival (16.7 vs. 45.1%, p = 0.017). Conclusion: This is the first report of a TERT promoter mutations in HNSCC patients from South America. The high prevalence of TERT mutation, as well as its association with poor disease-free survival and overall survival, particular at C228T locus might serve as a prognostic biomarker in HNSCC to help clinicians in the management of treatment.

No abstract