Expression level of Pre B cell leukemia homeobox 2 correlates with poor prognosis of gastric adenocarcinoma and esophageal squamous cell carcinoma

Pre B cell leukemia homeobox 2 (PBX2), a member of PBX family, acts as a co-factor of homeobox proteins to regulate proliferation and differentiation of tumor cells. Our recent study revealed prognostic significance of PBX2 expression in non-small cell lung carcinoma. The significance of PBX2 expression was examined in cases with gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC), and the role of PBX2 in tumor behavior was evaluated in GC and ESCC cell lines of knocked-down PBX2 expression. Expression level of PBX2 was immunohistochemically examined in 94 patients of GC and 64 patients of ESCC. Staining intensity for PBX2 was categorized as equal to or stronger (level 1) and weaker (level 2) than that of endothelial cells. Cases with level 1 expression in more than 20% of tumor were defined as high and others low expression. Patients with low PBX2 expression showed a better prognosis than those with high expression in both GC and ESCC. Multivariate analysis revealed PBX2 expression to be an independent prognosticator for both GC and ESCC. Knocked-down expression of PBX2 in GC and ESCC cell lines resulted in decrease of in vitro colony formation and in vivo tumorigenic activities, but proliferative and invasive activities did not change. Under serum depletion, apoptotic cell proportion was higher in PBX2 knocked-down cells than in control cells. The knock-down of PBX2 reduced Bcl-2 expression. Taken together, the high expression level of PBX2 was an independent negative prognosticator for both GC and ESCC, and PBX2 might promote tumor growth through suppression of apoptosis.