Ubiquitin-specific protease 14 expression associated with intrahepatic cholangiocarcinoma cell differentiation

The purpose of this study was to identify the gene alterations amplified from AO16 primer and examine whether the expression patterns of USP14 in clinical specimens from patients with intrahepatic cholangiocarcinoma (ICC) is associated with cancer cells. DNA from tumor and corresponding normal tissues of 52 patients was amplified with 33 arbitrary primers. The DNA fragment that altered most frequently in ICC was cloned, sequenced, and identified by comparison with known nucleotide sequences in the genome database. The DNA copy numbers of the allelic alterations in cholangiocarcinoma were determined by quantitative real-time PCR and interpreted as allelic loss or DNA amplification by comparison with the reference gene. Associations between allelic imbalance and clinicopathological parameters of ICC patients were evaluated by X²-tests. The Kaplan-Meier method was used to analyze survival rates. Immunohistochemically, USP14 showed weak cytoplasmic staining in normal bile duct epithelial cells. It was strongly detected in 21 cancer patients (43.8%). There were correlations between USP14 expression level and the clinicopathological features of ICC, histological grade (P < 0.05). However, there were no significant differences in age, gender, tumor size, metastasis, lymph node metastasis, and staging. USP14 expression was related to cholangiocarcinoma cell differentiation. Due to their emerging role in control of multiple signaling pathways and oncoproteins, USP14 inhibitors may be useful for anticancer agents.