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 colorectal liver metastases 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.

Once colorectal cancer spreads to the liver, it becomes much more deadly, despite advances in treatment. Could there be a way to predict survival for these cancers? These authors investigated the protein h-prune, which is associated with tumor aggressiveness. When they analyzed specimens of colorectal liver tumor metastases, they found h-prune in 28% of cases, and these had poorer survival than patients whose tumors lacked h-prune. In cell culture, h-prune promoted cell motility and boosted production of proteins involved in metastasis, while in mice it increased tumor invasiveness. Thus, h-prune could be a valuable prognostic tool or therapeutic target. This article is protected by copyright. All rights reserved.

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