Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance.
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 TXA2level of 1000 pg/mL was selected as a practical cutoff point, 95% of CRC patients were successfully identified. Further study suggested that the TXA2pathway is constitutively activated during colorectal tumorigenesis and required for anchorage-independent growth of colon cancer cells.


CONCLUSIONS
This study established the importance of the TXA2pathway in CRC pathophysiology, and laid the groundwork for introducing a TXA2-targeting strategy to CRC prevention, early detection and management.
Hormel Institute, University of Minnesota, Austin, Minnesota, USA ; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, P.R. China.
Haitao
H
Li
China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, P.R. China ; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China ; Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.
Kangdong
K
Liu
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Lisa A
LA
Boardman
Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.
Yuzhou
Y
Zhao
Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Lei
L
Wang
Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Yuqiao
Y
Sheng
Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Naomi
N
Oi
Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Paul J
PJ
Limburg
Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Ann M
AM
Bode
Hormel Institute, University of Minnesota, Austin, Minnesota, USA ; China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, P.R. China.
Zigang
Z
Dong
colorectal cancer; familial adenomatous polyposis; thromboxane A2