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Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade

Yixuan Gong, Li Wang, Haocheng Yu, Naomi Alpert, Mitchell D. Cohen, Colette Prophete, Lori Horton, Maureen Sisco, Sung-Hyun Park, Hyun-Wook Lee, Judith Zelikoff, Lung-Chi Chen, Mayte Suarez-Farinas, Michael J. Donovan, Stuart A. Aaronson, Matthew Galsky, Jun Zhu, Emanuela Taioli and William K. Oh
Yixuan Gong
Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
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Li Wang
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.Sema4, a Mount Sinai Venture, Stamford, Connecticut.
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Haocheng Yu
Sema4, a Mount Sinai Venture, Stamford, Connecticut.
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Naomi Alpert
Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York.
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Mitchell D. Cohen
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
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Colette Prophete
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
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Lori Horton
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
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Maureen Sisco
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
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Sung-Hyun Park
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
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Hyun-Wook Lee
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
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Judith Zelikoff
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
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Lung-Chi Chen
Nelson Institute of Environmental Medicine, New York University, Tuxedo Park, New York.
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Mayte Suarez-Farinas
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
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Michael J. Donovan
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
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Stuart A. Aaronson
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
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Matthew Galsky
Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
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Jun Zhu
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.Sema4, a Mount Sinai Venture, Stamford, Connecticut.
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Emanuela Taioli
Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York.
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  • For correspondence: william.oh@mssm.edu emanuela.taioli@mountsinai.org
William K. Oh
Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
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  • For correspondence: william.oh@mssm.edu emanuela.taioli@mountsinai.org
DOI: 10.1158/1541-7786.MCR-19-0115
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  • Correction: Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade - August 1, 2019

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Abstract

An excess incidence of prostate cancer has been identified among World Trade Center (WTC) responders. In this study, we hypothesized that WTC dust, which contained carcinogens and tumor-promoting agents, could facilitate prostate cancer development by inducing DNA damage, promoting cell proliferation, and causing chronic inflammation. We compared expression of immunologic and inflammatory genes using a NanoString assay on archived prostate tumors from WTC Health Program (WTCHP) patients and non-WTC patients with prostate cancer. Furthermore, to assess immediate and delayed responses of prostate tissue to acute WTC dust exposure via intratracheal inhalation, we performed RNA-seq on the prostate of normal rats that were exposed to moderate to high doses of WTC dust. WTC prostate cancer cases showed significant upregulation of genes involved in DNA damage and G2–M arrest. Cell-type enrichment analysis showed that Th17 cells, a subset of proinflammatory Th cells, were specifically upregulated in WTC patients. In rats exposed to WTC dust, we observed upregulation of gene transcripts of cell types involved in both adaptive immune response (dendritic cells and B cells) and inflammatory response (Th17 cells) in the prostate. Unexpectedly, genes in the cholesterol biosynthesis pathway were also significantly upregulated 30 days after acute dust exposure. Our results suggest that respiratory exposure to WTC dust can induce inflammatory and immune responses in prostate tissue.

Implications: WTC-related prostate cancer displayed a distinct gene expression pattern that could be the result of exposure to specific carcinogens. Our data warrant further epidemiologic and cellular mechanistic studies to better understand the consequences of WTC dust exposure.

Visual Overview: http://mcr.aacrjournals.org/content/early/2019/06/18/1541-7786.MCR-19-0115/F1.large.jpg.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).

  • Mol Cancer Res 2019;XX:XX–XX

  • Received January 31, 2019.
  • Revision received March 27, 2019.
  • Accepted May 20, 2019.
  • Published first June 20, 2019.
  • ©2019 American Association for Cancer Research.

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Published OnlineFirst June 20, 2019
doi: 10.1158/1541-7786.MCR-19-0115

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Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade
Yixuan Gong, Li Wang, Haocheng Yu, Naomi Alpert, Mitchell D. Cohen, Colette Prophete, Lori Horton, Maureen Sisco, Sung-Hyun Park, Hyun-Wook Lee, Judith Zelikoff, Lung-Chi Chen, Mayte Suarez-Farinas, Michael J. Donovan, Stuart A. Aaronson, Matthew Galsky, Jun Zhu, Emanuela Taioli and William K. Oh
Mol Cancer Res June 20 2019 DOI: 10.1158/1541-7786.MCR-19-0115

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Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade
Yixuan Gong, Li Wang, Haocheng Yu, Naomi Alpert, Mitchell D. Cohen, Colette Prophete, Lori Horton, Maureen Sisco, Sung-Hyun Park, Hyun-Wook Lee, Judith Zelikoff, Lung-Chi Chen, Mayte Suarez-Farinas, Michael J. Donovan, Stuart A. Aaronson, Matthew Galsky, Jun Zhu, Emanuela Taioli and William K. Oh
Mol Cancer Res June 20 2019 DOI: 10.1158/1541-7786.MCR-19-0115
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Molecular Cancer Research
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