Oropharyngeal squamous cell carcinoma (SCC) is strongly associated with human papillomavirus (HPV) infection, which is distinctively different from most other head and neck cancers. However, a robust quantitative reverse transcription PCR (RT‐qPCR) method for comprehensive expression profiling of HPV genes in routinely fixed tissues has not been reported. To address this issue, we have established a new real‐time RT‐PCR method for the expression profiling of the E6 and E7 oncogenes from 13 high‐risk HPV types. This method was validated in cervical cancer and by comparison with another HPV RNA detection method (in situ hybridization) in oropharyngeal tumors. In addition, the expression profiles of selected HPV‐related human genes were also analyzed. HPV E6 and E7 expression profiles were then analyzed in 150 archived oropharyngeal SCC samples and compared with other variables and with patient outcomes. Our study showed that RT‐qPCR and RNA in situ hybridization were 100% concordant in determining HPV status. HPV transcriptional activity was found in most oropharyngeal SCC (81.3%), a prevalence that is higher than in previous studies. Besides HPV16, three other HPV types were also detected, including 33, 35 and 18. Furthermore, HPV and p16 had essentially identical expression signatures, and both HPV and p16 were prognostic biomarkers for the prediction of disease outcome. Thus, p16 mRNA or protein expression signature is a sensitive and specific surrogate marker for HPV transcriptional activity (all genotypes combined).
The impairment of wound healing in diabetic patients is an important clinical problem affecting millions of patients worldwide. Various clinical and basic science studies show that stem cell therapy, as a regenerative medical therapy, can be a good solution. In this paper, we begin with an introduction of the cellular mechanism of the diabetic ulcer. We will then discuss the advantages and limitations of various stem cell therapies that have been under extensive recent study.
BACKGROUND
Oropharyngeal squamous cell carcinoma (SCC) rates have been increasing significantly in recent years, despite a decreasing incidence of head and neck cancer in general. Oropharyngeal cancer has many characteristics that are distinctively different from other head and neck cancers, and thus it is important to focus specifically on cancers arising here, with the goal of improving patient outcomes. One important goal is to identify patients who are likely to fail standard therapy and who could potentially benefit from alternative or targeted treatments.
METHODS
In this study, we evaluated the prognostic value of microRNAs (miRNAs) in oropharyngeal SCC. miRNAs are small non-coding RNAs that are master regulators of many important biological processes. In total, 150 oropharyngeal tumors were analyzed using our recently developed quantitative PCR-based method for miRNA expression profiling. In addition, the expression of miRNAs was also correlated to human papillomavirus (HPV) transcriptional activities.
RESULTS AND CONCLUSION
Our study identified six miRNAs that were significantly associated with cancer survival. A combined expression signature of these miRNAs was prognostic of oropharyngeal SCC, independent of common clinical features or HPV status. Importantly, this new miRNA signature was experimentally validated in an independent oropharyngeal SCC cohort. Furthermore, five HPV-related miRNAs were identified which may help to characterize HPV-induced cancers including both oropharyngeal and cervical SCC.
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