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Sci Rep. 2019 Nov 18;9(1):16965. doi: 10.1038/s41598-019-53268-1.

Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma.

Author information

1
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA. kate.poropatich@northwestern.edu.
2
Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. kate.poropatich@northwestern.edu.
3
Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. kate.poropatich@northwestern.edu.
4
Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
5
Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
6
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
7
Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
8
Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
9
X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL, 60439, USA.
10
Northwestern University Pathology Core Facility, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
11
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Abstract

Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is biologically distinct from HPV-negative HNSCC. Outside of HPV-status, few tumor-intrinsic variables have been identified that correlate to improved survival. As part of exploratory analysis into the trace elemental composition of oropharyngeal squamous cell carcinoma (OPSCC), we performed elemental quanitification by X-ray fluorescence microscopy (XFM) on a small cohort (n = 32) of patients with HPV-positive and -negative OPSCC and identified in HPV-positive cases increased zinc (Zn) concentrations in tumor tissue relative to normal tissue. Subsequent immunohistochemistry of six Zn-binding proteins-zinc-α2-glycoprotein (AZGP1), Lipocalin-1, Albumin, S100A7, S100A8 and S100A9-revealed that only AZGP1 expression significantly correlated to HPV-status (p < 0.001) and was also increased in tumor relative to normal tissue from HPV-positive OPSCC tumor samples. AZGP1 protein expression in our cohort significantly correlated to a prolonged recurrence-free survival (p = 0.029), similar to HNSCC cases from the TCGA (n = 499), where highest AZGP1 mRNA levels correlated to improved overall survival (p = 0.023). By showing for the first time that HPV-positive OPSCC patients have increased intratumoral Zn levels and AZGP1 expression, we identify possible positive prognostic biomarkers in HNSCC as well as possible mechanisms of increased sensitivity to chemoradiation in HPV-positive OPSCC.

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