Cornelia Lerner1, Silke Wemmert2, Florian Bochen2, Philipp Kulas2, Maximilian Linxweiler2, Andrea Hasenfus3, Joana Heinzelmann4, Petra Leidinger5, Christina Backes5, Eckart Meese5, Steffi Urbschat6, Bernhard Schick2. 1. Department of Otolaryngology, Saarland University Medical Center, Homburg/Saar, Germany. Cornelia.Lerner@uks.eu. 2. Department of Otolaryngology, Saarland University Medical Center, Homburg/Saar, Germany. 3. Department of Pathology, Saarland University Medical Center, Homburg/Saar, Germany. 4. Department of Urology and Pediatric Urology, Saarland University Medical Center, Homburg/Saar, Germany. 5. Institute of Human Genetics, Saarland University, Homburg/Saar, Germany. 6. Department of Neurosurgery, Saarland University Medical Center, Homburg/Saar, Germany.
Abstract
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide with an unchanged 5-year survival rate during the last decade. To detect reliable prognostic markers and improve patients' outcome in future, the aim of our study was to detect differences in microRNA (miRNA; miR) expression profile and further on to analyze the functional role of selected miRNAs. METHODS: Blood samples from HNSCC patients and sex- and age-matched healthy volunteers were analyzed by microarrays and validated by quantitative real-time PCR. Data were compared with tumor tissue results and all findings were correlated with clinical parameters. Additionally, the proliferation and migration potential of two cell lines transfected with miRNA mimics and inhibitors for miR-146a and miR-155 were examined. RESULTS: Initial analysis of blood samples showed no significant differences between the miRNA profile of HNSCC patients and healthy controls (p > 0.05). Interestingly, down-regulation of miR-146a and miR-155 in blood of patients correlated with the occurrence of distant metastasis regarding tumor patients only (p = 0.023 and p = 0.028, respectively). Additionally, our investigations in tissue samples revealed a lower expression of miR-155 in tumor cells (p = 0.003) and a correlation with higher cT-classification for down-regulation of miR-146a (p = 0.005). Moreover, functional assays demonstrated that inhibition of miR-146a and miR-155 promoted dramatically proliferation and migration potential, whereas transfection of both mimics had an inhibitory effect. CONCLUSIONS: Characterizing the expression of miR-146a and miR-155 and their functional role in tumor biology underlined significantly their proliferation and migration potential suggesting relevance as potential prognostic markers in HNSCC.
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide with an unchanged 5-year survival rate during the last decade. To detect reliable prognostic markers and improve patients' outcome in future, the aim of our study was to detect differences in microRNA (miRNA; miR) expression profile and further on to analyze the functional role of selected miRNAs. METHODS: Blood samples from HNSCC patients and sex- and age-matched healthy volunteers were analyzed by microarrays and validated by quantitative real-time PCR. Data were compared with tumor tissue results and all findings were correlated with clinical parameters. Additionally, the proliferation and migration potential of two cell lines transfected with miRNA mimics and inhibitors for miR-146a and miR-155 were examined. RESULTS: Initial analysis of blood samples showed no significant differences between the miRNA profile of HNSCC patients and healthy controls (p > 0.05). Interestingly, down-regulation of miR-146a and miR-155 in blood of patients correlated with the occurrence of distant metastasis regarding tumorpatients only (p = 0.023 and p = 0.028, respectively). Additionally, our investigations in tissue samples revealed a lower expression of miR-155 in tumor cells (p = 0.003) and a correlation with higher cT-classification for down-regulation of miR-146a (p = 0.005). Moreover, functional assays demonstrated that inhibition of miR-146a and miR-155 promoted dramatically proliferation and migration potential, whereas transfection of both mimics had an inhibitory effect. CONCLUSIONS: Characterizing the expression of miR-146a and miR-155 and their functional role in tumor biology underlined significantly their proliferation and migration potential suggesting relevance as potential prognostic markers in HNSCC.
Entities:
Keywords:
Blood; Head and neck squamous cell carcinoma; Metastasis; microRNA
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