PLA2G2A expression and its clinical significance in colorectal tumors

Abstract

PLA2 groupIIA (PLA2G2A), the secreted Phospholipase A2 (PLA2) is expressed in human Paneth cells, lacrimal glands, chondrocytes and amniotic epithelial cells. Induction of PLA2G2A is a frequent feature of inflammatory responses. Its mouse homolog, Mom1 can decrease the number and size of intestinal tumor formation in the ApcMin/+ mouse. In our previous cDNA microarray analysis, the expression of PLA2G2A was found to be associated with prolonged survival and less frequent metastasis in gastric adenocarcinoma (Proc. Natl. Acad. Sci. USA 2002; 99:16203-8). The aim of this study was to explore the possible clinical significance of PLA2G2A expression in colorectal cancer, and to compare the expression levels with normal mucosa and adenoma. Using tissue microarray containing colorectal cancer, adenoma and normal mucosa, the expression of PLA2G2A was assessed by non-radioactive in-situ hybridization. Control hybridization with β-actin was performed to ensure RNA integrity. High level expression of PLA2G2A was detected in 67% normal mucosa (n=100), 71% adenoma (n=59) and 33% colorectal cancer (n=187). The proportion of colorectal cancer expressing high level PLA2G2A is significantly lower compared with adenoma and normal mucosa (p<0.0001). Comparison of 74 paired colorectal cancer with their corresponding normal mucosa also showed a significantly lower level of PLA2G2A expression in the cancers (Wilcoxon Signed Ranked Test, p=0.002). High expression of PLA2G2A was associated with less advanced tumor stage (r=0.159, p=0.03) and poor differentiation (r=0.266, p<0.001). Patients whose tumors expressing high level of PLA2G2A demonstrated significantly extended survival (75% at 3rd and 5th year) compared to the low expression group (53% and 45% at 3rd and 5th year, p=0.01). Also PLA2G2A expression was associated with prolonged disease free survival (p=0.016). We concluded that the loss of PLA2G2A expression occurred predominantly from the transition of colorectal adenoma to carcinoma and PLA2G2A might function in suppressing tumor progression and metastasis in the colon.