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

Kate Poropatich; Tatjana Paunesku; Alia Zander; Brian Wray; Matthew Schipma; Prarthana Dalal; Mark Agulnik; Si Chen; Barry Lai; Olga Antipova; Evan Maxey; Koshonna Brown; Michael Beau Wanzer; Demirkan Gursel; Hanli Fan; Alfred Rademaker; Gayle E. Woloschak; Bharat B. Mittal

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

Kate Poropatich^*, Tatjana Paunesku, Alia Zander, Brian Wray, Matthew Schipma, Prarthana Dalal, Mark Agulnik, Si Chen, Barry Lai, Olga Antipova, Evan Maxey, Koshonna Brown, Michael Beau Wanzer, Demirkan Gursel, Hanli Fan, Alfred Rademaker, Gayle E. Woloschak, Bharat B. Mittal

^*Corresponding author for this work

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

12 Scopus citations

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.

Original language	English (US)
Article number	16965
Journal	Scientific reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-53268-1
State	Published - Dec 1 2019

Funding

The research was funded by the Family of Walter Neumann and the 2018 Northwestern Lurie Cancer Center Research Innovation Challenge Award (supported by the IDP Foundation and the Sherman Fairchild Foundation). Work at the Advanced Photon Source at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences contract DE-AC02-06CH11357. This work was also supported by the Northwestern University Pathology Core Facility and a Cancer Center Support Grant (NCI CA060553) with help from Bernice Frederick, Bella Shmaltsuyeva and Shanshan Zhang Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569; authors would especially like to thank the facility director Dr. Young Ah Goo for her assistance with proteomics analysis. Additional thanks are extended to Germaine Elbohy for her assistance with clinical outcome data. Finally, we are grateful to Tiffany Ge for her help with protein zinc content queries.

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Poropatich, K., Paunesku, T., Zander, A., Wray, B., Schipma, M., Dalal, P., Agulnik, M., Chen, S., Lai, B., Antipova, O., Maxey, E., Brown, K., Wanzer, M. B., Gursel, D., Fan, H., Rademaker, A., Woloschak, G. E., & Mittal, B. B. (2019). Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma. Scientific reports, 9(1), Article 16965. https://doi.org/10.1038/s41598-019-53268-1

@article{c79f3f7b97c9468ea7e8e5b5f2453bcd,

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-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.",

author = "Kate Poropatich and Tatjana Paunesku and Alia Zander and Brian Wray and Matthew Schipma and Prarthana Dalal and Mark Agulnik and Si Chen and Barry Lai and Olga Antipova and Evan Maxey and Koshonna Brown and Wanzer, \{Michael Beau\} and Demirkan Gursel and Hanli Fan and Alfred Rademaker and Woloschak, \{Gayle E.\} and Mittal, \{Bharat B.\}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41598-019-53268-1",

language = "English (US)",

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Poropatich, K, Paunesku, T, Zander, A, Wray, B, Schipma, M, Dalal, P, Agulnik, M, Chen, S, Lai, B, Antipova, O, Maxey, E, Brown, K, Wanzer, MB, Gursel, D, Fan, H, Rademaker, A , Woloschak, GE & Mittal, BB 2019, 'Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma', Scientific reports, vol. 9, no. 1, 16965. https://doi.org/10.1038/s41598-019-53268-1

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T1 - Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

AU - Poropatich, Kate

AU - Paunesku, Tatjana

AU - Zander, Alia

AU - Wray, Brian

AU - Schipma, Matthew

AU - Dalal, Prarthana

AU - Agulnik, Mark

AU - Chen, Si

AU - Lai, Barry

AU - Antipova, Olga

AU - Maxey, Evan

AU - Brown, Koshonna

AU - Wanzer, Michael Beau

AU - Gursel, Demirkan

AU - Fan, Hanli

AU - Rademaker, Alfred

AU - Woloschak, Gayle E.

AU - Mittal, Bharat B.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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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VL - 9

JO - Scientific reports

JF - Scientific reports

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ER -

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

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