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 1000 pg/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.

• Authors: Haitao Li, Kangdong Liu, Lisa A Boardman, Yuzhou Zhao, Lei Wang, Yuqiao Sheng, Naomi Oi, Paul J Limburg, Ann M Bode, Zigang Dong
• Journal: EBioMedicine (EBioMedicine) Vol. 2 Issue 2 Pg. 165-171 (Feb 01 2015) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 25750933 (Publication Type: Journal Article)