h-Prune is associated with poor prognosis and epithelial-mesenchymal transition in patients with colorectal liver metastases.
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.
['Hashimoto|Masakazu|M|', 'Kobayashi|Tsuyoshi|T|', 'Tashiro|Hirotaka|H|', 'Arihiro|Koji|K|', 'Kikuchi|Akira|A|', 'Ohdan|Hideki|H|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000818:Animals D014408:Biomarkers, Tumor D002352:Carrier Proteins D045744:Cell Line, Tumor D002465:Cell Movement D015179:Colorectal Neoplasms D004195:Disease Models, Animal D058750:Epithelial-Mesenchymal Transition D005260:Female D006801:Humans D007150:Immunohistochemistry D008113:Liver Neoplasms D008297:Male D051379:Mice D008875:Middle Aged D060787:Neoplasm Grading D009362:Neoplasm Metastasis D010744:Phosphoric Monoester Hydrolases D011379:Prognosis D055815:Young Adult
h-prune epithelial-mesenchymal transition colorectal liver metastasis metastasis colorectal cancer