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.

Oxylipins associated with colorectal cancer

“…Eicosanoids produced by COX-2 that have been implicated in the development and progression of CRC include pro-tumorigenic prostaglandin E2; prostaglandin D2, although the opinion on their effects are conflicting (Murata & Maehara, 2016). The elevated levels of thromboxane A2 may possibly be used as a diagnostic CRC biomarker (Li et al, 2015). COX-2 is overexpressed in CRC tissue during adenoma-carcinoma sequence.…”

A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology

“…These data reaffirm that AA is absolutely required in order to maintain normal cell function. Interestingly, excess AA in cell membranes may have a detrimental effect, as exhibited by the positive correlation between AA-derived PGE 2 , TXA 2 and colon cancer risk (3, 30, 31). …”

“…Elevated levels of cyclooxygenase 2 (COX2) and concomitant overproduction of prostaglandins of the 2-series, e.g., PGE 2 and TXA 2 , are often detected in human colon adenomas and adenocarcinomas (2, 3). From a physiological perspective, AA-derived eicosanoids, including PGE 2 are diverse, and have been shown to stimulate key downstream signaling cascades that regulate cell proliferation, apoptosis, angiogenesis, inflammation, and immune surveillance (4, 5).…”

Complex roles of the old drug aspirin in cancer chemoprevention and therapy

“…COX catalyzes the production of prostaglandins such as prostaglandin E2 (PGE2), prostaglandin D2, and thromboxane A2 (TXA2), which trigger pain, inflammation, fever, or blood clotting. Activation of COX1 in platelets leads to the production of TXA 2 and platelet activation . COX is a direct target of aspirin.…”