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Because we showed that integration neither affects the levels of viral genes, nor those of virally disrupted human genes, a genome\u2010wide screen was performed to identify human genes which expression is influenced by viral integration and have clinical relevance. Thirty\u2010three fresh\u2010frozen HPV\u201016 positive OPSCC samples with known integration status were analyzed by mRNA expression profiling. Among the genes of interest, Aldo\u2010keto\u2010reductases 1C1 and 1C3 (AKR1C1, AKR1C3) were upregulated in tumors with viral integration. Additionally, 141 OPSCC, including 48 HPV\u2010positive cases, were used to validate protein expression by immunohistochemistry. Results were correlated with clinical and histopathological data. Non\u2010hierarchical 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 <jats:italic>p<\/jats:italic> &lt;0.0001), both in HPV\u2010positive (<jats:italic>p<\/jats:italic> \u22640.001) and \u2010negative (<jats:italic>p<\/jats:italic> \u22640.017) tumors. OPSCC with integrated HPV16 show upregulation of AKR1C1 and AKR1C3 expression, which strongly correlates with poor survival rates. Also in HPV\u2010negative tumors, upregulation of these proteins correlates with unfavorable outcome. Deregulated AKR1C expression has also been observed in other tumors, making these genes promising candidates to indicate prognosis. In addition, the availability of inhibitors of these gene products may be utilized for drug treatment.<\/jats:p>","DOI":"10.1002\/ijc.31954","type":"journal-article","created":{"date-parts":[[2018,10,27]],"date-time":"2018-10-27T07:45:32Z","timestamp":1540626332000},"page":"2465-2477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Upregulation of AKR1C1 and AKR1C3 expression in OPSCC with integrated HPV16 and HPV\u2010negative tumors is an indicator of poor prognosis"],"prefix":"10.1002","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-1218","authenticated-orcid":false,"given":"Christian U.","family":"Huebbers","sequence":"first","affiliation":[{"name":"Jean\u2010Uhrmacher\u2010Institute for Otorhinolaryngological Research University of Cologne  Cologne 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