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CUL4A overexpression as an independent adverse prognosticator in intrahepatic cholangiocarcinoma
- Source :
- BMC Cancer, Vol 17, Iss 1, Pp 1-10 (2017), BMC Cancer
- Publication Year :
- 2017
- Publisher :
- BMC, 2017.
-
Abstract
- Background CUL4A has been known for its oncogenic properties in various human cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA) has not been explored. Methods 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. Results 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. Conclusions 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.
- Subjects :
- Adult
Male
0301 basic medicine
Cancer Research
Immunohistochemical study
Disease-free survival
Apoptosis
lcsh:RC254-282
Cholangiocarcinoma
03 medical and health sciences
0302 clinical medicine
Surgical oncology
Cell Line, Tumor
Biomarkers, Tumor
Genetics
Humans
Medicine
Neoplasm Invasiveness
Intrahepatic Cholangiocarcinoma
Aged
Cell Proliferation
Intrahepatic cholangiocarcinoma
Aged, 80 and over
Cisplatin
Tissue microarray
business.industry
Cell growth
Middle Aged
Cullin Proteins
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
Tissue Array Analysis
Cell culture
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
CUL4A
Female
business
Migration and invasion assays
Research Article
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....e17d47164ac7970b7509d9be1a4e1d11