Circulating prostaglandins as biomarkers for colorectal cancer?

Despite increases in our understanding of intestinal tumour biology, (FAP, an inherited predisposition to colorectal tumour formation due colorectal cancer remains a leading cause of cancer-related death worldwide. Most colorectal cancers develop from benign adenomas, presenting an opportunity for early detection and intervention prior to the onset of malignancy. For patients with early-stage tumours, fiveyear survival rates are high. However, as early-stage tumours are typically asymptomatic, strategies to identify at risk individuals are critical to enable early detection. Therefore, a key challenge is improving (the currently suboptimal) patient uptake to screening programmes, as well as the development of good prognostic and predictive biomarkers for cancer risk and response to treatment. In this context and because of the well-established role of prostaglandins in colorectal tumorigenesis there are an increasing number of studies evaluating the utility of circulating prostaglandins in association with cancer risk and disease progression. In this issue of EBioMedicine, Li et al. (2015) provide evidence suggesting that the measurement of circulating prostaglandins in the blood may have potential utility in identifying patients at risk of developing, or with, colorectal cancer. This is an attractive premise, as a convenient blood-based test may increase uptake amongst eligible individuals that do not presently participate in current screening procedures (such as the faecal occult blood test). Prostaglandins are well-known to cancer biologists and have attracted a lot of attention as important targets for chemoprevention (Chan et al., 2005). They are generated by cyclooxygenase (COX) enzymes (COX-1 and COX-2), which are targets of non-steroidal antiinflammatory drugs (NSAIDs) such as aspirin. COX-2 is known to be upregulated in a size-dependent manner in about half of colorectal adenomas and in the majority of colorectal cancers, leading to increased PGE2 levels (Eberhart et al., 1994; Elder et al., 2002). PGE2 has a major influence on colorectal tumour biology (Greenhough et al., 2009), and the chemopreventive action of NSAIDs is thought to be mediated, at least in part, by blocking PGE2 production. A number of studies have highlighted that PGE-M, a urinary PGE2metabolite that reflects systemic PGE2 levels, could serve as a prognostic biomarker in colorectal, gastric, and more recently breast cancers (Dong et al., 2009; Johnson et al., 2006; Wang and DuBois, 2013). At present, it is not clear whether prostaglandins other than PGE-M could also serve as prognostic or predictive biomarkers for colorectal cancer. To examine this, Li et al. took blood samples from healthy individuals, as well as from patients with familial adenomatous polyposis