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, Dana Hashim, Mayte Suarez-Farinas, Michael J. Donovan, Stuart A. Aaronson, Matthew Galsky, Jun Zhu, Emanuela Taioli, William K. Oh

Research output: Contribution to journalArticle

1 Citation (Scopus)

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/molcanres/17/8/1605/F1.large.jpg.

Original languageEnglish (US)
Pages (from-to)1605-1612
Number of pages8
JournalMolecular cancer research : MCR
Volume17
Issue number8
DOIs
StatePublished - Aug 1 2019
Externally publishedYes

Fingerprint

Dust
Prostatic Neoplasms
Prostate
Th17 Cells
Carcinogens
Genes
DNA Damage
Up-Regulation
Adaptive Immunity
Dendritic Cells
Inhalation
Neoplasms
B-Lymphocytes
Cholesterol
Cell Proliferation
RNA
Inflammation
Gene Expression
Incidence
Health

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade. / Gong, Yixuan; Wang, Li; Yu, Haocheng; Alpert, Naomi; Cohen, Mitchell D.; Prophete, Colette; Horton, Lori; Sisco, Maureen; Park, Sung Hyun; Lee, Hyun Wook; Zelikoff, Judith; Chen, Lung Chi; Hashim, Dana; Suarez-Farinas, Mayte; Donovan, Michael J.; Aaronson, Stuart A.; Galsky, Matthew; Zhu, Jun; Taioli, Emanuela; Oh, William K.

In: Molecular cancer research : MCR, Vol. 17, No. 8, 01.08.2019, p. 1605-1612.

Research output: Contribution to journalArticle

Gong, Y, Wang, L, Yu, H, Alpert, N, Cohen, MD, Prophete, C, Horton, L, Sisco, M, Park, SH, Lee, HW, Zelikoff, J, Chen, LC, Hashim, D, Suarez-Farinas, M, Donovan, MJ, Aaronson, SA, Galsky, M, Zhu, J, Taioli, E & Oh, WK 2019, 'Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade', Molecular cancer research : MCR, vol. 17, no. 8, pp. 1605-1612. https://doi.org/10.1158/1541-7786.MCR-19-0115
Gong, Yixuan ; Wang, Li ; Yu, Haocheng ; Alpert, Naomi ; Cohen, Mitchell D. ; Prophete, Colette ; Horton, Lori ; Sisco, Maureen ; Park, Sung Hyun ; Lee, Hyun Wook ; Zelikoff, Judith ; Chen, Lung Chi ; Hashim, Dana ; Suarez-Farinas, Mayte ; Donovan, Michael J. ; Aaronson, Stuart A. ; Galsky, Matthew ; Zhu, Jun ; Taioli, Emanuela ; Oh, William K. / Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade. In: Molecular cancer research : MCR. 2019 ; Vol. 17, No. 8. pp. 1605-1612.
@article{78e5586f53c241a9b6e7c827846fbfaf,
title = "Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade",
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/molcanres/17/8/1605/F1.large.jpg.",
author = "Yixuan Gong and Li Wang and Haocheng Yu and Naomi Alpert and Cohen, {Mitchell D.} and Colette Prophete and Lori Horton and Maureen Sisco and Park, {Sung Hyun} and Lee, {Hyun Wook} and Judith Zelikoff and Chen, {Lung Chi} and Dana Hashim and Mayte Suarez-Farinas and Donovan, {Michael J.} and Aaronson, {Stuart A.} and Matthew Galsky and Jun Zhu and Emanuela Taioli and Oh, {William K.}",
year = "2019",
month = "8",
day = "1",
doi = "10.1158/1541-7786.MCR-19-0115",
language = "English (US)",
volume = "17",
pages = "1605--1612",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Prostate Cancer in World Trade Center Responders Demonstrates Evidence of an Inflammatory Cascade

AU - Gong, Yixuan

AU - Wang, Li

AU - Yu, Haocheng

AU - Alpert, Naomi

AU - Cohen, Mitchell D.

AU - Prophete, Colette

AU - Horton, Lori

AU - Sisco, Maureen

AU - Park, Sung Hyun

AU - Lee, Hyun Wook

AU - Zelikoff, Judith

AU - Chen, Lung Chi

AU - Hashim, Dana

AU - Suarez-Farinas, Mayte

AU - Donovan, Michael J.

AU - Aaronson, Stuart A.

AU - Galsky, Matthew

AU - Zhu, Jun

AU - Taioli, Emanuela

AU - Oh, William K.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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/molcanres/17/8/1605/F1.large.jpg.

AB - 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/molcanres/17/8/1605/F1.large.jpg.

UR - http://www.scopus.com/inward/record.url?scp=85071055889&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071055889&partnerID=8YFLogxK

U2 - 10.1158/1541-7786.MCR-19-0115

DO - 10.1158/1541-7786.MCR-19-0115

M3 - Article

C2 - 31221798

AN - SCOPUS:85071055889

VL - 17

SP - 1605

EP - 1612

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 8

ER -