Modeling of cancer-related body-wide effects identifies LTB4 as a diagnostic biomarker for pancreatic cancer
Jiang, Shu-Heng ; Liu, Dejun ; Hu, Li-Peng ; Zhang, Shan ; Yu, Yanqiu ; Sun, Yong-Wei ; Ji, Jianguang LU
and Zhang, Zhi-Gang
(2022)
In EBioMedicine
80.
p.104050-104050
- Abstract
BACKGROUND: Cancer elicits a complex adaptive response in an organism. Limited information is available for the body-wide effects induced by cancer. Here, we evaluated multiorgan changes in mouse models of pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions (pancreatic intraepithelial neoplasia, PanIN) to decipher changes that occur during PDAC development.
METHODS: RNA-sequencing was employed in the brain, colon, stomach, kidney, heart, liver, and lung tissues of mice with PanIN and PDAC. A combination of differential expression analysis and functional-category enrichment was applied for an in-depth understanding of the multiorgan transcriptome. Differentially expressed genes were verified by quantitative real-time... (More)
BACKGROUND: Cancer elicits a complex adaptive response in an organism. Limited information is available for the body-wide effects induced by cancer. Here, we evaluated multiorgan changes in mouse models of pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions (pancreatic intraepithelial neoplasia, PanIN) to decipher changes that occur during PDAC development.
METHODS: RNA-sequencing was employed in the brain, colon, stomach, kidney, heart, liver, and lung tissues of mice with PanIN and PDAC. A combination of differential expression analysis and functional-category enrichment was applied for an in-depth understanding of the multiorgan transcriptome. Differentially expressed genes were verified by quantitative real-time polymerase chain reaction. Neutrophil and macrophage infiltration in multiple organs was analyzed by immunohistochemical staining. Leukotriene B4 (LTB4) levels in mouse and human serum samples were determined by enzyme-linked immunosorbent assay.
FINDINGS: Transcriptional changes within diverse organs during PanIN and PDAC stages were identified. Using Gene Ontology enrichment analysis, increased neutrophil infiltration was discovered as a central and prominent affected feature, which occurred in the liver, lung, and stomach at the PanIN stage. The brain appeared to be well protected from the sequels of PanIN or PDAC. Importantly, serum LTB4 was able to discriminate PDAC from normal controls, chronic pancreatitis, and intraductal papillary mucinous neoplasms with high performance.
INTERPRETATION: Our study provides a high-resolution cartographic view of the dynamic multiorgan transcriptomic landscape of mice with PDAC and its precursor lesions. Our findings suggest that LTB4 could serve as a biomarker for the early detection of PDAC.
FUNDING: The complete list of funders can be found in the Acknowledgement section.
(Less)
- author
- Jiang, Shu-Heng
; Liu, Dejun
; Hu, Li-Peng
; Zhang, Shan
; Yu, Yanqiu
; Sun, Yong-Wei
; Ji, Jianguang
LU
and Zhang, Zhi-Gang
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- EBioMedicine
- volume
- 80
- article number
- 104050
- pages
- 104050 - 104050
- publisher
- Elsevier
- external identifiers
-
- pmid:35561453
- scopus:85129910504
- ISSN
- 2352-3964
- DOI
- 10.1016/j.ebiom.2022.104050
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
- id
- fbc07a34-98f8-4f20-b15f-5e6604ab0e11
- date added to LUP
- 2022-05-19 10:48:35
- date last changed
- 2024-06-27 18:49:49
@article{fbc07a34-98f8-4f20-b15f-5e6604ab0e11,
abstract = {{<p>BACKGROUND: Cancer elicits a complex adaptive response in an organism. Limited information is available for the body-wide effects induced by cancer. Here, we evaluated multiorgan changes in mouse models of pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions (pancreatic intraepithelial neoplasia, PanIN) to decipher changes that occur during PDAC development.</p><p>METHODS: RNA-sequencing was employed in the brain, colon, stomach, kidney, heart, liver, and lung tissues of mice with PanIN and PDAC. A combination of differential expression analysis and functional-category enrichment was applied for an in-depth understanding of the multiorgan transcriptome. Differentially expressed genes were verified by quantitative real-time polymerase chain reaction. Neutrophil and macrophage infiltration in multiple organs was analyzed by immunohistochemical staining. Leukotriene B4 (LTB4) levels in mouse and human serum samples were determined by enzyme-linked immunosorbent assay.</p><p>FINDINGS: Transcriptional changes within diverse organs during PanIN and PDAC stages were identified. Using Gene Ontology enrichment analysis, increased neutrophil infiltration was discovered as a central and prominent affected feature, which occurred in the liver, lung, and stomach at the PanIN stage. The brain appeared to be well protected from the sequels of PanIN or PDAC. Importantly, serum LTB4 was able to discriminate PDAC from normal controls, chronic pancreatitis, and intraductal papillary mucinous neoplasms with high performance.</p><p>INTERPRETATION: Our study provides a high-resolution cartographic view of the dynamic multiorgan transcriptomic landscape of mice with PDAC and its precursor lesions. Our findings suggest that LTB4 could serve as a biomarker for the early detection of PDAC.</p><p>FUNDING: The complete list of funders can be found in the Acknowledgement section.</p>}},
author = {{Jiang, Shu-Heng and Liu, Dejun and Hu, Li-Peng and Zhang, Shan and Yu, Yanqiu and Sun, Yong-Wei and Ji, Jianguang and Zhang, Zhi-Gang}},
issn = {{2352-3964}},
language = {{eng}},
pages = {{104050--104050}},
publisher = {{Elsevier}},
series = {{EBioMedicine}},
title = {{Modeling of cancer-related body-wide effects identifies LTB4 as a diagnostic biomarker for pancreatic cancer}},
url = {{http://dx.doi.org/10.1016/j.ebiom.2022.104050}},
doi = {{10.1016/j.ebiom.2022.104050}},
volume = {{80}},
year = {{2022}},
}