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Int J Mol Sci. 2018 Mar 25;19(4). pii: E978. doi: 10.3390/ijms19040978.

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

Author information

1
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. torbjorn.ramqvist@ki.se.
2
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. anders.nasman@ki.se.
3
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. bo.franzen@ki.se.
4
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. cinzia.bersani@ki.se.
5
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 171 77 Stockholm, Sweden. andrej.alekseenko@scilifelab.se.
6
National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, 17121 Solna, Sweden. andrej.alekseenko@scilifelab.se.
7
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. susanne.becker@ki.se.
8
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. linnea.haeggblom@ki.se.
9
Department of Clinical Science and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. aeneas.kolev@sll.se.
10
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. tina.dalianis@ki.se.
11
Department of Clinical Science and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden. eva.munck-afrosenschold-wikland@sll.se.

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.

KEYWORDS:

base of tongue cancer; clinical outcome; human papillomavirus; oropharyngeal cancer; protein expression; proximity extension assay; tonsillar cancer

PMID:
29587383
PMCID:
PMC5979357
DOI:
10.3390/ijms19040978
[Indexed for MEDLINE]
Free PMC Article

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