Evaluation Challenges in the Validation of B7-H3 as Oral Tongue Cancer Prognosticator
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ORIGINAL PAPER
Evaluation Challenges in the Validation of B7-H3 as Oral Tongue Cancer Prognosticator Meri Sieviläinen1,2 · Anna Maria Wirsing3 · Aini Hyytiäinen1,2 · Rabeia Almahmoudi1,2 · Priscila Rodrigues4,5 · Inger‑Heidi Bjerkli3,6 · Pirjo Åström4,5 · Sanna Toppila‑Salmi7 · Timo Paavonen8 · Ricardo D. Coletta9 · Elin Hadler‑Olsen3,10 · Tuula Salo1,2,4,5,11 · Ahmed Al‑Samadi1,2 Received: 19 July 2020 / Revised: 31 August 2020 / Accepted: 3 September 2020 © The Author(s) 2020
Abstract B7-H3 was the only molecule identified with prognostic potential from a recent systematic review of the prognostic value of immune checkpoints in oral cancer. We aimed to validate this finding in a multicenter international cohort. We retrospectively retrieved 323 oral tongue squamous cell carcinoma (OTSCC) samples from three different countries (Brazil, Finland, and Norway) for immunostaining and scoring for B7-H3. We evaluated tumor immunogenicity by analyzing the amount of tumor-infiltrating lymphocytes and divided the tumors into immune hot and cold. To increase the reliability of the results, both digital and manual visual scoring were used. Survival curves were constructed based on the Kaplan-Meier method, and the Cox proportional hazard model was utilized for univariate and multivariate survival analysis. B7-H3 expression was not significantly associated with overall or disease-specific survival in the whole OTSCC cohort. When divided into immune hot and cold tumors, high B7-H3 expression was significantly associated with poor disease-specific and overall survival in the immune hot group, depending on the scoring method and the country of the cohort. This was achieved only in the univariate analysis. In conclusion, B7-H3 was a negative prognosticator for OTSCC patient survival in the subgroup of immune hot tumors, and was not validated as a prognosticator in the full cohort. Our findings suggest that the immune activity of the tumor should be considered when testing immune checkpoints as biomarkers. Keywords Oral tongue squamous cell carcinoma · B7-H3 · Tumor infiltrating lymphocytes · Immune checkpoint · Replication crisis. Aini Hyytiäinen and Rabeia Almahmoudi have contributed equally to this manuscript Electronic supplementary material The online version of this article (doi:https://doi.org/10.1007/s12105-020-01222-3) contains supplementary material, which is available to authorized users. * Ahmed Al‑Samadi ahmed.al‑[email protected] 1
Introduction The incidence of oral together with lip squamous cell carcinoma (OSCC) is unfortunately increasing. In 2018, the number of new cases worldwide was approximately 350,000 6
Department of Otorhinolaryngology, University Hospital of North Norway, Tromsø, Norway
7
Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
8
Department of Pathology, Faculty of Medicine and Health Technology and Fimlab laboratories, Tampere University and Tampere University Hospital, Tampere, Finland
Department of Oral Diagnosis, Pi
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