TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma

Sanni Tuominen; Linda Nissi; Antti Kukkula; Johannes Routila; Teemu Huusko; Ilmo Leivo; Heikki Minn; Heikki Irjala; Eliisa Löyttyniemi; Sami Ventelä; Maria Sundvall; Tove J Grönroos

doi:10.3389/fonc.2023.1298333

TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma

Front Oncol. 2023 Dec 14:13:1298333. doi: 10.3389/fonc.2023.1298333. eCollection 2023.

Authors

Sanni Tuominen^{1

2

3

4}, Linda Nissi⁵, Antti Kukkula^{2

3}, Johannes Routila⁶, Teemu Huusko⁶, Ilmo Leivo⁷, Heikki Minn⁵, Heikki Irjala⁶, Eliisa Löyttyniemi⁸, Sami Ventelä⁶, Maria Sundvall^#^{2

3

5}, Tove J Grönroos^#^{1

4

5}

Affiliations

¹ Preclinical Imaging Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
² Cancer Research Unit, Institute of Biomedicine, University of Turku, Turku, Finland.
³ FICAN West Cancer Research Laboratory, Turku University Hospital and University of Turku, Turku, Finland.
⁴ Medicity Research Laboratory, Faculty of Medicine, University of Turku, Turku, Finland.
⁵ Department of Clinical Oncology, Turku University Hospital and University of Turku, Turku, Finland.
⁶ Department of Otorhinolaryngology - Head and Neck Surgery, Turku University Hospital and University of Turku, Turku, Finland.
⁷ Department of Pathology, Turku University Hospital and University of Turku, Turku, Finland.
⁸ Department of Biostatistics, Turku University Hospital and University of Turku, Turku, Finland.

^# Contributed equally.

Abstract

Background: Treatment resistance and relapse are common problems in head and neck squamous cell carcinoma (HNSCC). Except for p16, no clinically accepted prognostic biomarkers are available for HNSCC. New biomarkers predictive of recurrence and survival are crucial for optimal treatment planning and patient outcome. High translocator protein (TSPO) levels have been associated with poor survival in cancer, but the role of TSPO has not been extensively evaluated in HNSCC.

Materials and methods: TSPO expression was determined in a large population-based tissue microarray cohort including 611 patients with HNSCC and evaluated for survival in several clinicopathological subgroups. A TCGA HNSCC cohort was used to further analyze the role of TSPO in HNSCC.

Results: TSPO expression was downregulated in more aggressive tumors. Low TSPO expression associated with worse 5-year survival and was an independent prognostic factor for disease-specific survival. Subgroup analyses showed that low TSPO expression associated with worse survival particularly in p16-positive oropharyngeal cancer. In silico analyses supported the prognostic role of TSPO. Cellular respiration had the highest significance in pathway analyses for genes expressed positively with TSPO.

Conclusion: Decreased TSPO expression associates with poor prognosis in HNSCC. TSPO is a prognostic biomarker in HNSCC to potentially guide treatment stratification especially in p16-positive oropharyngeal cancer.

Keywords: biomarker; head and neck cancer; immune landscape; oxidative phosphorylation; p16; translocator protein.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was financially supported by the Swedish Cultural Foundation in Finland (TG) 177117; Swedish Cultural Foundation in Finland (ST) 176805; Finnish Cultural Foundation Satakunta Regional Fund (ST) 75202354; Finnish Cultural Foundation Häme Regional Fund (LN) 15212321; Emil Aaltonen Foundation (LN) 210146 K; Governmental Research Funding for Turku University Hospital (TG) T41701/13142; Maud Kuistila Memorial Foundation (ST) 2020-0217F; Turku University Foundation (TG) 080854; Research Council of Finland (TG) 357468.