Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance

Haitao Li; Kangdong Liu; Lisa A. Boardman; Yuzhou Zhao; Lei Wang; Yuqiao Sheng; Naomi Oi; Paul J. Limburg; Ann M. Bode; Zigang Dong

doi:10.1016/j.ebiom.2014.12.004

Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance

Haitao Li, Kangdong Liu, Lisa A. Boardman, Yuzhou Zhao, Lei Wang, Yuqiao Sheng, Naomi Oi, Paul J. Limburg, Ann M. Bode, Zigang Dong

Gastroenterology and Hepatology

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

16 Scopus citations

Abstract

Background: Colorectal cancer (CRC) represents the third leading cause of cancer-related death in the United States. Lack of reliable biomarkers remains a critical issue for early detection of CRC. In this study, we investigated the potential predictive values of circulating prostaglandin (PG) biosynthesis in CRC risk. Methods: Profiles of circulating PG biosynthesis and platelet counts were determined in healthy subjects (n = 16), familial adenomatous polyposis (FAP) patients who were classified as regular aspirin users (n = 14) or nonusers (n = 24), and CRC patients with (n = 18) or without FAP history (n = 20). Immunohistochemistry staining was performed on biopsy samples. Results: Analysis of circulating PG biosynthesis unexpectedly revealed that CRC progression is accompanied by a pronounced elevation of circulating thromboxane A₂ (TXA₂) levels. When a circulating TXA₂ level of 1000pg/mL was selected as a practical cutoff point, 95% of CRC patients were successfully identified. Further study suggested that the TXA₂ pathway is constitutively activated during colorectal tumorigenesis and required for anchorage-independent growth of colon cancer cells. Conclusions: This study established the importance of the TXA₂ pathway in CRC pathophysiology, and laid the groundwork for introducing a TXA₂-targeting strategy to CRC prevention, early detection and management.

Original language	English (US)
Pages (from-to)	165-171
Number of pages	7
Journal	EBioMedicine
Volume	2
Issue number	2
DOIs	https://doi.org/10.1016/j.ebiom.2014.12.004
State	Published - Feb 2015

Keywords

Colorectal cancer
Familial adenomatous polyposis
Thromboxane A

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.ebiom.2014.12.004

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@article{f0ee26b3e9204ddab3061ca20995c7d1,

title = "Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance",

abstract = "Background: Colorectal cancer (CRC) represents the third leading cause of cancer-related death in the United States. Lack of reliable biomarkers remains a critical issue for early detection of CRC. In this study, we investigated the potential predictive values of circulating prostaglandin (PG) biosynthesis in CRC risk. Methods: Profiles of circulating PG biosynthesis and platelet counts were determined in healthy subjects (n = 16), familial adenomatous polyposis (FAP) patients who were classified as regular aspirin users (n = 14) or nonusers (n = 24), and CRC patients with (n = 18) or without FAP history (n = 20). Immunohistochemistry staining was performed on biopsy samples. Results: Analysis of circulating PG biosynthesis unexpectedly revealed that CRC progression is accompanied by a pronounced elevation of circulating thromboxane A2 (TXA2) levels. When a circulating TXA2 level of 1000pg/mL was selected as a practical cutoff point, 95% of CRC patients were successfully identified. Further study suggested that the TXA2 pathway is constitutively activated during colorectal tumorigenesis and required for anchorage-independent growth of colon cancer cells. Conclusions: This study established the importance of the TXA2 pathway in CRC pathophysiology, and laid the groundwork for introducing a TXA2-targeting strategy to CRC prevention, early detection and management.",

keywords = "Colorectal cancer, Familial adenomatous polyposis, Thromboxane A",

author = "Haitao Li and Kangdong Liu and Boardman, {Lisa A.} and Yuzhou Zhao and Lei Wang and Yuqiao Sheng and Naomi Oi and Limburg, {Paul J.} and Bode, {Ann M.} and Zigang Dong",

note = "Funding Information: We acknowledge the support from Mayo Clinic Center for Cell Signaling in Gastroenterology ( NIDDK P30DK084567 ). We thank Ms. Cindy Nordyke for the technical assistance in clinical tissue processing and Ms. Nicki Brickman at The Hormel Institute, University of Minnesota for the assistance in submitting our manuscript. Publisher Copyright: {\textcopyright} 2014.",

year = "2015",

month = feb,

doi = "10.1016/j.ebiom.2014.12.004",

language = "English (US)",

volume = "2",

pages = "165--171",

journal = "EBioMedicine",

issn = "2352-3964",

publisher = "Elsevier BV",

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TY - JOUR

T1 - Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance

AU - Li, Haitao

AU - Liu, Kangdong

AU - Boardman, Lisa A.

AU - Zhao, Yuzhou

AU - Wang, Lei

AU - Sheng, Yuqiao

AU - Oi, Naomi

AU - Limburg, Paul J.

AU - Bode, Ann M.

AU - Dong, Zigang

N1 - Funding Information: We acknowledge the support from Mayo Clinic Center for Cell Signaling in Gastroenterology ( NIDDK P30DK084567 ). We thank Ms. Cindy Nordyke for the technical assistance in clinical tissue processing and Ms. Nicki Brickman at The Hormel Institute, University of Minnesota for the assistance in submitting our manuscript. Publisher Copyright: © 2014.

PY - 2015/2

Y1 - 2015/2

N2 - Background: Colorectal cancer (CRC) represents the third leading cause of cancer-related death in the United States. Lack of reliable biomarkers remains a critical issue for early detection of CRC. In this study, we investigated the potential predictive values of circulating prostaglandin (PG) biosynthesis in CRC risk. Methods: Profiles of circulating PG biosynthesis and platelet counts were determined in healthy subjects (n = 16), familial adenomatous polyposis (FAP) patients who were classified as regular aspirin users (n = 14) or nonusers (n = 24), and CRC patients with (n = 18) or without FAP history (n = 20). Immunohistochemistry staining was performed on biopsy samples. Results: Analysis of circulating PG biosynthesis unexpectedly revealed that CRC progression is accompanied by a pronounced elevation of circulating thromboxane A2 (TXA2) levels. When a circulating TXA2 level of 1000pg/mL was selected as a practical cutoff point, 95% of CRC patients were successfully identified. Further study suggested that the TXA2 pathway is constitutively activated during colorectal tumorigenesis and required for anchorage-independent growth of colon cancer cells. Conclusions: This study established the importance of the TXA2 pathway in CRC pathophysiology, and laid the groundwork for introducing a TXA2-targeting strategy to CRC prevention, early detection and management.

AB - Background: Colorectal cancer (CRC) represents the third leading cause of cancer-related death in the United States. Lack of reliable biomarkers remains a critical issue for early detection of CRC. In this study, we investigated the potential predictive values of circulating prostaglandin (PG) biosynthesis in CRC risk. Methods: Profiles of circulating PG biosynthesis and platelet counts were determined in healthy subjects (n = 16), familial adenomatous polyposis (FAP) patients who were classified as regular aspirin users (n = 14) or nonusers (n = 24), and CRC patients with (n = 18) or without FAP history (n = 20). Immunohistochemistry staining was performed on biopsy samples. Results: Analysis of circulating PG biosynthesis unexpectedly revealed that CRC progression is accompanied by a pronounced elevation of circulating thromboxane A2 (TXA2) levels. When a circulating TXA2 level of 1000pg/mL was selected as a practical cutoff point, 95% of CRC patients were successfully identified. Further study suggested that the TXA2 pathway is constitutively activated during colorectal tumorigenesis and required for anchorage-independent growth of colon cancer cells. Conclusions: This study established the importance of the TXA2 pathway in CRC pathophysiology, and laid the groundwork for introducing a TXA2-targeting strategy to CRC prevention, early detection and management.

KW - Colorectal cancer

KW - Familial adenomatous polyposis

KW - Thromboxane A

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JO - EBioMedicine

JF - EBioMedicine

IS - 2

ER -

Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance

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