The shapes of the funnel plots showed that a low potential for publication bias (Figure 4). Moreover, we used an influence analysis to evaluate the influence

of single study on the summary effect. The meta-analysis was not dominated by any individual study, and removing any study at a time made no difference. Figure 4 Funnel plot of studies of Cdx2 positivity in gastric cancer. Discussion Gastric cancer is a markedly heterogeneous disease in histologic feature and biological characters, especially in the advanced stages [32]. A number of clinical studies revealing its biological behavior and prognosis could be significantly different among patients at the same stages and with the Epigenetics Compound Library manufacturer same histological types or differentiation grades [33–35]. Thus, it is important to find a biomarker to indicate the biological characters and predict the outcome of patients with gastric carcinoma. Since their original identification

in Drosophila, the selleck products caudal related homologues (Cdx1 and Cdx2) have been known to be involved in the regulation of proliferation and differentiation of intestinal epithelial cells [36]. Cdx2 was bound to the Cdx1 promoter region in the intestinal metaplasia and the normal intestine, and upregulated the transcriptional activity of the Cdx1 gene in the human gastric carcinoma [37]. Thus, Cdx2, as a member of this gene family, is crucial for Cdx-dependent program. In adults, the structural and functional overexpression of Cdx2 in tumors, compared with normal mucosa, suggests that Cdx2 could play a pivotal L-NAME HCl role in the development of intestinal metaplasia [17]. The implication of Cdx2 in intestinal metaplasia has been demonstrated in the intestinal metaplasia of the stomach where Cdx2 was ectopically overexpressed, suggesting that it could play a major role during intestinal metaplasia formation in the stomach [17]. Intestinal metaplasia has been shown to be a precursor of intestinal-type gastric adenocarcinoma. Long-term intestinal metaplasia induced gastric adenocarcinoma in the Cdx2-transgenic mouse stomach and no significant changes were noted in wild-type littermate [38]. The tumor incidence was 100% at 100 weeks after birth

[39]. It can be concluded that Cdx2 expression was a precursor of gastric carcinoma and served as a reliable tumor marker in gastric cancer. Whether Cdx2-positive expression could be considered as a prognostic factor for gastric cancer patients is still in dispute at the present time. Several investigators reported that Cdx2 reduced cell proliferation rates, and Cdx2-positive expression was decreased p38 MAPK inhibitors clinical trials progressively with the depth of tumor invasion and advancing stage of gastric cancer [9, 14, 40]. They indicated that Cdx2 was an independent prognostic indicator for gastric carcinoma. However, other studies showed that no significant correlation could be determined between Cdx2 and clinicopathological parameters such as tumoe size, invasion and metastasis of lymph node in gastric cancer [12, 15, 24].