PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients: a systematic review.

BACKGROUND Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed. METHODS Using terms for PTGS2 and colorectal cancer, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled HRs [95% confidence intervals (CI)] for the association between PTGS2 expression and tumor recurrence, colorectal cancer-specific survival, and overall survival. RESULTS In total, 29 studies, which had prognostic data on 5,648 patients, met the inclusion criteria. PTGS2-positive patients were at an increased risk of tumor recurrence (n = 9 studies; HR, 2.79; 95% CI, 1.76-4.41; P < 0.001) and had poorer colorectal cancer-specific survival (n = 7; HR, 1.36; 95% CI, 1.02-1.82; P = 0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancer-specific survival but less so for recurrence. PTGS2 expression was not associated with overall survival [(n = 16; pooled unadjusted HR, 1.30; 95% CI, 0.94-1.79; P = 0.11) and (n = 9; pooled adjusted HR, 1.02; 95% CI, 0.72-1.45; P = 0.91)]. CONCLUSIONS PTGS2 expression was associated with an increased risk of tumor recurrence and poorer colorectal cancer-specific survival but not overall survival among patients with colorectal cancer. However, confounding by tumor characteristics such as tumor stage seems likely. IMPACT There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in patients with colorectal cancer. Furthermore, studies providing adjusted results are required.