h-Prune is associated with poor prognosis and epithelial–mesenchymal transition in patients with colorectal liver metastases

Abstract

The prognosis of patients with colorectal liver metastases (CRLM) remains low despite advances in chemotherapy and surgery. The expression of h-prune (human homolog of Drosophila prune protein; HGNC13420), an exopolyphosphatase, is correlated with progression and aggressiveness in several cancers and promotes migration and invasion. We investigated the role of h-prune in CRLM. To investigate the role of h-prune, immunohistochemical analysis for h-prune was performed in 87 surgically resected specimens of CRLM obtained between 2001 and 2009 at the Hiroshima University Hospital. Immunohistochemical analysis revealed positive staining for h-prune in 24 (28%) cases. The overall survival rate was significantly lower in h-prune-positive cases than in h-prune-negative cases (p = 0.003). Multivariate analysis showed that h-prune positivity was the only independent factor related to poor overall survival of patients after curative hepatectomy of CRLM. In vitro and in vivo, h-prune-knocked-down and h-prune-overexpressing cells were analyzed. In vitro, h-prune was associated with increased cell motility and upregulation of epithelial–mesenchymal transition (EMT) markers. In a mouse model, h-prune was associated with invasion of the tumor and distant metastases. In summary, h-prune expression is a useful marker to identify high-risk patients for resectable colorectal liver metastasis. h-Prune expression is necessary for cancer cell motility and EMT and is associated with liver and lung metastasis in colorectal cancer cells. h-Prune could be a new prognostic marker and molecular target for CRLM.