microRNA-329 suppresses epithelial-to-mesenchymal transition and lymph node metastasis in bile duct cancer by inhibiting laminin subunit beta 3.

Bile duct cancer (BDC), also known as cholangiocarcinoma, is a highly desmoplastic cancer with a growth pattern characterized by periductal extension and infiltration. Studies have suggested that microRNAs (miRNAs) play an important role in BDC progression. Here we aim at investigating the effects of miR-329 on BDC development, focusing especially on epithelial-to-mesenchymal transition (EMT) in vitro and lymph node metastasis in vivo. Expression microarrays associated with BDC tissues were collected and differentially expressed genes were analyzed, followed by miRNA target prediction and verification. The role miR-329 played in BDC was examined using gain-of-function and loss-of-function methods. The expressions of miR-329, laminin subunit beta 3 (LAMB3), and EMT markers, in addition to cell proliferation, migration, and invasion were evaluated. Furthermore, nude mice models of BDC were established to observe tumor growth and metastatic lymph nodes. The LAMB3 was identified as an upregulated gene based on the GSE77984 and GSE45001 microarray analysis. LAMB3 was also predicted and confirmed to be a target gene of miR-329 by dual-luciferase reporter assay. Through further cell experiments, the EMT process was reversed, cell proliferation, invasion, and migration were suppressed, when miR-329 was upregulated. Furthermore, in vivo experiments exhibited that the overexpression of miR-329 inhibited tumor growth and the number of metastatic lymph nodes. This study provides in vivo and in vitro evidence that miR-329 inhibits BDC progression through translational repression of LAMB3. Therefore, the obtained results may aid as an experimental basis for improving prognosis of BDC.

Outcomes of non-anatomic liver resection for hepatocellular carcinoma in the patients with liver cirrhosis and analysis of prognostic factors.

PURPOSE: In the east countries, patients with hepatocellular carcinoma (HCC) are usually associated with varied degrees of liver cirrhosis, and anatomic resection is therefore limited to use, especially in those with severe liver cirrhosis. This study aims to evaluate the clinical value of non-anatomic resection in HCC patients with cirrhosis. METHODS: Seventy-seven consecutive HCC patients with cirrhosis underwent non-anatomic liver resection in Tongji Hospital from January 2003 to December 2006. The clinical data, severity of liver cirrhosis, and survival rates of these patients were retrospectively evaluated, and the prognostic factors were analyzed. RESULTS: One-, 2-, and 3-year overall and disease-free survival rates of this cohort of patients were 78%, 68%, 56%, and 66%, 58%, 55%, respectively. The hospital mortality and morbidity were 0% and 24.7%, respectively. The 1-, 2-, and 3-year overall survival rates were 85.7%, 77.1%, and 74.3% in the patients with mild cirrhosis, 81.5%, 63%, and 48.1% in the patients with moderate cirrhosis, and 60.0%, 53.3%, and 26.7% in the patients with severe cirrhosis, respectively. There was a significant difference among the patients with different grades of cirrhosis (P = 0.001). Multivariate and univariate analyses revealed that severity of cirrhosis, tumor diameter larger than 5 cm, and vascular invasion were independent prognostic factors. CONCLUSIONS: Non-anatomic liver resection for HCC could yield comparable outcomes with anatomic resection in the patients with mild cirrhosis or tumors diameter smaller than 5 cm. Severity of cirrhosis is an independent factor worsening long-time survival. Non-anatomic resection is a safe and effective surgical modality in the treatment of HCC patients with cirrhosis.