CUL4A overexpression as an independent adverse prognosticator in intrahepatic cholangiocarcinoma

• Published in: BMC cancer Vol. 17; no. 1; p. 395
• Main Authors: Huang, Gong -Kai, Liu, Ting-Ting, Weng, Shao-Wen, You, Huey-Ling, Wei, Yu-Ching, Chen, Chang-Han, Eng, Hock-Liew, Huang, Wan-Ting
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.06.2017; BioMed Central; BMC
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis - genetics; Biliary tract cancer; Biomarkers, Tumor - genetics; Cancer; Care and treatment; Cell cycle; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - genetics; Cholangiocarcinoma; Cholangiocarcinoma - genetics; Cholangiocarcinoma - pathology; Cisplatin; CUL4A; Cullin Proteins - genetics; Deoxyribonucleic acid; Disease-Free Survival; DNA; Expression vectors; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Humans; Immunohistochemical study; Intrahepatic cholangiocarcinoma; Male; Medical prognosis; Metastasis; Middle Aged; Migration and invasion assays; Mobility; Multivariate analysis; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Oncogenes; Patients; Physiological aspects; Physiology; Prognosis; Proteins; Signal transduction; Survival; Tissue Array Analysis; Tumors; Taiwan; United States > US; CUL4A; Immunohistochemical study; Migration and invasion assays; Disease-free survival; Intrahepatic cholangiocarcinoma
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-017-3389-z

CUL4A has been known for its oncogenic properties in various human cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA) has not been explored. We retrospectively investigated 105 iCCA cases from a single medical institution. Tissue microarrays were used for immunohistochemical analysis of CUL4A expression. CUL4A expression vectors were introduced in cell lines. Cell migration and invasion assays were used to compare the mobility potential of iCCA cells under basal conditions and after manipulation. Then we evaluated the effects of CUL4A on the cell growth by proliferation assay, and further checked the susceptibility to cisplatin in iCCA cells with or without CUL4A overexpression. CUL4A overexpression was detected in 34 cases (32.4%). Patients with CUL4A-overexpressing tumors exhibited shortened disease-free survival (mean, 27.7 versus 90.4 months; P = 0.011). In the multivariate analysis model, CUL4A overexpression was shown to be an independent unfavorable predictor for disease-free survival (P = 0.045). Moreover, stably transfected CUL4A-overexpressing iCCA cell lines displayed an increased mobility potential and enhanced cell growth without impact on susceptibility to cisplatin. Our data demonstrate that overexpression of CUL4A plays an oncogenic role in iCCA and adversely affects disease-free survival. Thus, it may prove to be a powerful prognostic factor and a potential therapeutic target.