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Int. J. Mol. Sci. 2018, 19(4), 978; https://doi.org/10.3390/ijms19040978

Protein Expression in Tonsillar and Base of Tongue Cancer and in Relation to Human Papillomavirus (HPV) and Clinical Outcome

1
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden
2
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 171 77 Stockholm, Sweden
3
National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, 17121 Solna, Sweden
4
Department of Clinical Science and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Received: 8 February 2018 / Revised: 15 March 2018 / Accepted: 22 March 2018 / Published: 25 March 2018
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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Abstract

Human papillomavirus (HPV) is a major etiological factor for tonsillar and the base of tongue cancer (TSCC/BOTSCC). HPV-positive and HPV-negative TSCC/BOTSCC present major differences in mutations, mRNA expression and clinical outcome. Earlier protein studies on TSCC/BOTSCC have mainly analyzed individual proteins. Here, the aim was to compare a larger set of cancer and immune related proteins in HPV-positive and HPV-negative TSCC/BOTSCC in relation to normal tissue, presence of HPV, and clinical outcome. Fresh frozen tissue from 42 HPV-positive and 17 HPV-negative TSCC/BOTSCC, and corresponding normal samples, were analyzed for expression of 167 proteins using two Olink multiplex immunoassays. Major differences in protein expression between TSCC/BOTSCC and normal tissue were identified, especially in chemo- and cytokines. Moreover, 34 proteins, mainly immunoregulatory proteins and chemokines, were differently expressed in HPV-positive vs HPV-negative TSCC/BOTSCC. Several proteins were potentially related to clinical outcome for HPV-positive or HPV-negative tumors. For HPV-positive tumors, these were mostly related to angiogenesis and hypoxia. Correlation with clinical outcome of one of these, VEGFA, was validated by immunohistochemistry. Differences in immune related proteins between HPV-positive and HPV-negative TSCC/BOTSCC reflect the stronger activity of the immune defense in the former. Angiogenesis related proteins might serve as potential targets for therapy in HPV-positive TSCC/BOTSCC. View Full-Text
Keywords: tonsillar cancer; base of tongue cancer; oropharyngeal cancer; human papillomavirus; proximity extension assay; clinical outcome; protein expression tonsillar cancer; base of tongue cancer; oropharyngeal cancer; human papillomavirus; proximity extension assay; clinical outcome; protein expression
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Ramqvist, T.; Näsman, A.; Franzén, B.; Bersani, C.; Alexeyenko, A.; Becker, S.; Haeggblom, L.; Kolev, A.; Dalianis, T.; Munck-Wikland, E. Protein Expression in Tonsillar and Base of Tongue Cancer and in Relation to Human Papillomavirus (HPV) and Clinical Outcome. Int. J. Mol. Sci. 2018, 19, 978.

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