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

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-alpha 2-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 chemoradiationmore » in HPV-positive OPSCC.« less

Authors:
 [1]; ORCiD logo [1];  [1];  [1];  [1];  [1];  [1];  [2];  [1];  [2];  [2];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Northwestern Univ., Evanston, IL (United States)
  2. Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH), National Cancer Institute; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1601427
Grant/Contract Number:  
[AC02-06CH11357]
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
[ Journal Volume: 9; Journal Issue: 1]; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Poropatich, Kate, Paunesku, Tatjana, Zander, Alia, Wray, Brian, Schipma, Matthew, Dalal, Prarthana, Agulnik, Mark, Chen, Si, Lai, Barry, Antipova, Olga, Maxey, Evan, Brown, Koshonna, Wanzer, Michael Beau, Gursel, Demirkan, Fan, Hanli, Rademaker, Alfred, Woloschak, Gayle E., and Mittal, Bharat B. Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma. United States: N. p., 2019. Web. doi:10.1038/s41598-019-53268-1.
Poropatich, Kate, Paunesku, Tatjana, Zander, Alia, Wray, Brian, Schipma, Matthew, Dalal, Prarthana, Agulnik, Mark, Chen, Si, Lai, Barry, Antipova, Olga, Maxey, Evan, Brown, Koshonna, Wanzer, Michael Beau, Gursel, Demirkan, Fan, Hanli, Rademaker, Alfred, Woloschak, Gayle E., & Mittal, Bharat B. Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma. United States. doi:10.1038/s41598-019-53268-1.
Poropatich, Kate, Paunesku, Tatjana, Zander, Alia, Wray, Brian, Schipma, Matthew, Dalal, Prarthana, Agulnik, Mark, Chen, Si, Lai, Barry, Antipova, Olga, Maxey, Evan, Brown, Koshonna, Wanzer, Michael Beau, Gursel, Demirkan, Fan, Hanli, Rademaker, Alfred, Woloschak, Gayle E., and Mittal, Bharat B. Mon . "Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma". United States. doi:10.1038/s41598-019-53268-1. https://www.osti.gov/servlets/purl/1601427.
@article{osti_1601427,
title = {Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma},
author = {Poropatich, Kate and Paunesku, Tatjana and Zander, Alia and Wray, Brian and Schipma, Matthew and Dalal, Prarthana and Agulnik, Mark and Chen, Si and Lai, Barry and Antipova, Olga and Maxey, Evan and Brown, Koshonna and Wanzer, Michael Beau and Gursel, Demirkan and Fan, Hanli and Rademaker, Alfred and Woloschak, Gayle E. and Mittal, Bharat B.},
abstractNote = {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-alpha 2-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.},
doi = {10.1038/s41598-019-53268-1},
journal = {Scientific Reports},
number = [1],
volume = [9],
place = {United States},
year = {2019},
month = {11}
}

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