Upregulation of AKR1C1 and AKR1C3 expression in OPSCC with integrated HPV16 and HPV-negative tumors is an indicator of poor prognosis
| Autor: | Jens Peter Klussmann, Oliver G. Siefer, Christian U. Huebbers, Bernd Kremer, Dirk Beutner, Femke Verhees, Ernst-Jan M. Speel, Emily A. Vucic, Leonard Poluschkin, Yueksel Korkmaz, Julia Seehawer, Wan L. Lam, Jutta Kolligs, Nadine C. Olthof, Mieke Henfling, Uta Drebber, Frans C. S. Ramaekers, Simon F. Preuss |
|---|---|
| Přispěvatelé: | Promovendi ODB, KNO, MUMC+: MA AIOS Keel Neus Oorheelkunde (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Genetica & Celbiologie, RS: GROW - R2 - Basic and Translational Cancer Biology, Moleculaire Celbiologie, MUMC+: Oncologie Centrum (3), MUMC+: MA Keel Neus Oorheelkunde (3), MUMC+: MA Keel Neus Oorheelkunde (9), Pathologie |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Cancer Research Genes Viral AKR1C1 Virus Integration Biology Genome PATHWAY 03 medical and health sciences DIPS-PCR 0302 clinical medicine Downregulation and upregulation Humans oxidative stress Clinical significance HEAD APOT-PCR 20-Hydroxysteroid Dehydrogenases Gene Survival analysis Human papillomavirus 16 viral integration Papillomavirus Infections HUMAN-PAPILLOMAVIRUS Aldo-Keto Reductase Family 1 Member C3 OROPHARYNGEAL CARCINOMA Middle Aged Prognosis CANCER Up-Regulation 3. Good health Survival Rate GENOME Oropharyngeal Neoplasms Oncology 030220 oncology & carcinogenesis DNA Viral immunohistochemistry Carcinoma Squamous Cell Cancer research SURVIVAL Immunohistochemistry Female Human genome Metabolic Networks and Pathways |
| Zdroj: | International Journal of Cancer, 144(10), 2465-2477. Wiley |
| ISSN: | 0020-7136 |
| Popis: | Different studies have shown that HPV16-positive OPSCC can be subdivided based on integration status (integrated, episomal and mixed forms). Because we showed that integration neither affects the levels of viral genes, nor those of virally disrupted human genes, a genome-wide screen was performed to identify human genes which expression is influenced by viral integration and have clinical relevance. Thirty-three fresh-frozen HPV-16 positive OPSCC samples with known integration status were analyzed by mRNA expression profiling. Among the genes of interest, Aldo-keto-reductases 1C1 and 1C3 (AKR1C1, AKR1C3) were upregulated in tumors with viral integration. Additionally, 141 OPSCC, including 48 HPV-positive cases, were used to validate protein expression by immunohistochemistry. Results were correlated with clinical and histopathological data. Non-hierarchical clustering resulted in two main groups differing in mRNA expression patterns, which interestingly corresponded with viral integration status. In OPSCC with integrated viral DNA, often metabolic pathways were deregulated with frequent upregulation of AKR1C1 and AKR1C3 transcripts. Survival analysis of 141 additionally immunostained OPSCC showed unfavorable survival rates for tumors with upregulation of AKR1C1 or AKR1C3 (both p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text