RESUMEN
PURPOSE: Oropharynx squamous cell carcinoma (OPSCC) is a subtype of head and neck squamous cell carcinoma (HNSCC) arising from the base of the tongue, lingual tonsils, tonsils, oropharynx or pharynx. The majority of HPV-positive OPSCCs has a good prognosis, but a fraction of them has a poor prognosis, similar to HPV-negative OPSCCs. An in-depth understanding of the molecular mechanisms underlying OPSCC is mandatory for the identification of novel prognostic biomarkers and/or novel therapeutic targets. METHODS: 14 HPV-positive and 15 HPV-negative OPSCCs with 5-year follow-up information were subjected to gene expression profiling and, subsequently, compared to three extensive published OPSCC cohorts to define robust biomarkers for HPV-negative lesions. Validation of Aldo-keto-reductases 1C3 (AKR1C3) by qRT-PCR was carried out on an independent cohort (n = 111) of OPSCC cases. In addition, OPSCC cell lines Fadu and Cal-27 were treated with Cisplatin and/or specific AKR1C3 inhibitors to assess their (combined) therapeutic effects. RESULTS: Gene set enrichment analysis (GSEA) on the four datasets revealed that the genes down-regulated in HPV-negative samples were mainly involved in immune system, whereas those up-regulated mainly in glutathione derivative biosynthetic and xenobiotic metabolic processes. A panel of 30 robust HPV-associated transcripts was identified, with AKR1C3 as top-overexpressed transcript in HPV-negative samples. AKR1C3 expression in 111 independent OPSCC cases positively correlated with a worse survival, both in the entire cohort and in HPV-positive samples. Pretreatment with a selective AKR1C3 inhibitor potentiated the effect of Cisplatin in OPSCC cells exhibiting higher basal AKR1C3 expression levels. CONCLUSIONS: We identified AKR1C3 as a potential prognostic biomarker in OPSCC and as a potential drug target whose inhibition can potentiate the effect of Cisplatin.
Asunto(s)
Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Orofaríngeas/metabolismo , Anciano , Anciano de 80 o más Años , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Regulación hacia Abajo/genética , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/complicaciones , Pronóstico , Regulación hacia Arriba/genéticaRESUMEN
Spontaneous epistaxis in patients with COVID-19 can represent a clinical challenge with respect to both the risk of contamination and the treatment options. We herein present the data of 30 patients with COVID-19 who developed spontaneous epistaxis while hospitalized at Eastern Piedmont Hospital during March and April 2020. All patients received low-molecular-weight heparin during their hospital stay and required supplementary oxygen therapy either by a nasal cannula or continuous positive airway pressure. Both conditions can represent risk factors for developing epistaxis. Prevention of crust formation in patients with rhinitis using a nasal lubricant should be recommended. If any treatment is required, appropriate self-protection is mandatory.