Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer

Michael Mints; David Landin; Anders Näsman; Leila Mirzaie; Ramona Gabriela Ursu; Mark Zupancic; Linda Marklund; Tina Dalianis; Eva Munck-Wikland; Torbjörn Ramqvist

doi:10.1038/s41598-020-80226-z

Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer

Michael Mints, David Landin, Anders Näsman, Leila Mirzaie, Ramona Gabriela Ursu, Mark Zupancic, Linda Marklund, Tina Dalianis, Eva Munck-Wikland, Torbjörn Ramqvist^*

^*Corresponding author for this work

Department of Molecular Cell Biology

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis. Local surgery may increase survival, but is often avoided due to significant post-op co-morbidities. Since prognostic markers are lacking, the aim was to find predictive biomarkers that identify patients whose response to oncological treatment is poor and who may benefit from primary surgery to increase survival. Pretreatment biopsies from 23 HPSCC patients, 3 human papillomavirus (HPV) positive and 20 HPV-negative, were analyzed for expression of 750 mRNAs using the Nanostring nCounter IO360 panel in relation to 3-year survival. Validation was performed through immunohistochemistry (IHC) for HLA class I and S100A12 in 74 HPV-negative HPSCC samples. Clustering identified a subset of HPV-negative HPSCC with favorable prognosis and a gene expression signature overexpressing calgranulins and immune genes, distinct from that of HPV-positive HPSCC. Enrichment analysis showed immune signaling, including the tumor inflammation signature, to be enriched in surviving patients. IHC validation confirmed high S100A12 and HLA class I expression to correlate with survival in HPV-negative HPSCC. This shows that immune activity is strongly related to survival in HPV-negative HPSCC. Enrichment of the tumor inflammation signature indicates a potential benefit of immunotherapy. Low expression of both HLA class I and S100A12 could be used to select patients for local surgery.

Original language	English
Article number	1782
Number of pages	11
Journal	Scientific Reports
Volume	11
Issue number	1
Early online date	19 Jan 2021
DOIs	https://doi.org/10.1038/s41598-020-80226-z
Publication status	Published - 19 Jan 2021

Funding

This work was supported by: The Cancer Society in Stockholm (151253, 181053), The Swedish Cancer Foundation (180440), The Stockholm County ALF (20180085, 2018037), Laryngfonden and the Cancer and Allergy Foundation (253). Anders Näsman was supported by Region Stockholm (clinical postdoctoral appointment). R.G. Ursu was supported by the University of Medicine and Pharmacy Grigore T Popa Iasi (6983/21.04.2020). The funding sources had no involvement in any part of the study. Contributions - Conception and design (TR, EMW, TD). Experimental procedures (AN, LM, TR, RU, MZ). Acquisition of clinical samples and clinical data (DL, LM, EMW). Analysis of data (MM, TR). Manuscript writing (MM, TR, EMW, TD).

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title = "Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer",

abstract = "Hypopharyngeal squamous cell carcinoma (HPSCC) has a very poor prognosis. Local surgery may increase survival, but is often avoided due to significant post-op co-morbidities. Since prognostic markers are lacking, the aim was to find predictive biomarkers that identify patients whose response to oncological treatment is poor and who may benefit from primary surgery to increase survival. Pretreatment biopsies from 23 HPSCC patients, 3 human papillomavirus (HPV) positive and 20 HPV-negative, were analyzed for expression of 750 mRNAs using the Nanostring nCounter IO360 panel in relation to 3-year survival. Validation was performed through immunohistochemistry (IHC) for HLA class I and S100A12 in 74 HPV-negative HPSCC samples. Clustering identified a subset of HPV-negative HPSCC with favorable prognosis and a gene expression signature overexpressing calgranulins and immune genes, distinct from that of HPV-positive HPSCC. Enrichment analysis showed immune signaling, including the tumor inflammation signature, to be enriched in surviving patients. IHC validation confirmed high S100A12 and HLA class I expression to correlate with survival in HPV-negative HPSCC. This shows that immune activity is strongly related to survival in HPV-negative HPSCC. Enrichment of the tumor inflammation signature indicates a potential benefit of immunotherapy. Low expression of both HLA class I and S100A12 could be used to select patients for local surgery.",

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Tumour inflammation signature and expression of S100A12 and HLA class I improve survival in HPV-negative hypopharyngeal cancer

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