@article{0b7daed04b404c27bf96f4e663879c30,
title = "Upregulation of AKR1C1 and AKR1C3 expression in OPSCC with integrated HPV16 and HPV-negative tumors is an indicator of poor prognosis",
abstract = "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",
keywords = "APOT-PCR, DIPS-PCR, viral integration, immunohistochemistry, oxidative stress, HUMAN-PAPILLOMAVIRUS, OXIDATIVE STRESS, OROPHARYNGEAL CARCINOMA, HEAD, CANCER, PATHWAY, GENOME, SURVIVAL",
author = "Huebbers, {Christian U.} and Femke Verhees and Leonard Poluschkin and Olthof, {Nadine C.} and Jutta Kolligs and Siefer, {Oliver G.} and Mieke Henfling and Ramaekers, {Frans C. S.} and Preuss, {Simon F.} and Dirk Beutner and Julia Seehawer and Uta Drebber and Yueksel Korkmaz and Lam, {Wan L.} and Vucic, {Emily A.} and Bernd Kremer and Klussmann, {Jens P.} and Speel, {Ernst-Jan M.}",
note = "Funding Information: Key words: APOT-PCR, DIPS-PCR, viral integration, immunohistochemistry, oxidative stress, AKR1C1, AKR1C3 Abbreviations: GO: gene-ontology; HPV: human papillomavirus; OPSCC: oropharyngeal squamous cell carcinoma; ROS: reactive oxygen species Additional Supporting Information may be found in the online version of this article. Conflict of interest: EJM Speel is funded by research grants from Novartis and Pfizer. All other authors declare no conflict of interest. Grant sponsor: Jean-Uhrmacher-Society; Grant number: n.a.; Grant sponsor: KoelnFortune, University of Cologne; Grant number: 40/2010; Grant sponsor: Jean Uhrmacher Foundation; Grant sponsor: Stiftung Tumorforschung Kopf-Hals; Grant number: N.A. DOI: 10.1002/ijc.31954 History: Received 7 Feb 2018; Accepted 9 Oct 2018; Online 27 Oct 2018 Correspondence to: Christian U. Huebbers, Ph.D., Jean-Uhrmacher-Institute for Otorhinolaryngological Research, University of Cologne, Geibelstrasse 29–31, 50,931 Cologne, Germany, Tel.: +49–221–478-97017, Fax: +49–221–478-97010, E-mail: christian.huebbers@uni-koeln.de Funding Information: The sponsors had no role in the study design, data collection, analysis and interpretation of the data, writing the article, and decision to submit the article for publication. Our study was supported by the Koeln Fortune Program, Faculty of Medicine, University of Cologne, Cologne, Germany (Grant number 40/2010 to CUH), the {\textquoteleft}Stiftung Tumorforschung Kopf-Hals{\textquoteright}, Wiesbaden, Germany (Grant to CUH) and the Jean Uhrmacher Foundation (Grant to CUH and DB), Cologne, Germany. Publisher Copyright: {\textcopyright} 2018 UICC",
year = "2019",
month = may,
day = "15",
doi = "10.1002/ijc.31954",
language = "English",
volume = "144",
pages = "2465--2477",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley",
number = "10",
}