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Int J Oncol. 2018 Jul;53(1):286-296. doi: 10.3892/ijo.2018.4383. Epub 2018 Apr 26.

Role of the overexpression of TRAF4 in predicting the prognosis of intrahepatic cholangiocarcinoma.

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Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Kunming Medical University, Kunming, Yunnan 650106, P.R. China.
Yunnan Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan 650031, P.R. China.
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Department of Orthodontics, School and Hospital of Stomatology, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.
School of Public Health, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.


The incidence of intrahepatic cholangiocarcinoma (ICC) is progressively increasing worldwide, and its prognosis remains poor. Accumulating evidence has demonstrated that tumor necrosis factor receptor-associated factor 4 (TRAF4), an adaptor protein, is involved in the carcinogenesis and progression of several tumor types. However, the function of TRAF4 in predicting prognosis, and mediating migration and invasion of ICC remains to be elucidated. In the present study, immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine that the expression of TRAF4 at the mRNA and protein levels in ICC tissues was significantly higher compared with that in non‑tumor tissues. The overexpression of TRAF4 was positively correlated with poor differentiation, regional lymphatic metastasis, and high tumor‑node-metastasis staging. Inhibiting the expression of TRAF4 using small interfering RNA decreased the migration and invasion of ICC cells in vitro. In addition, the AKT inhibitor perifosine eliminated the effect of TRAF4 on the invasion and migration of ICC cells in vitro. Clinically, the overexpression of TRAF4 was correlated with shorter overall survival rate and elevated recurrence rate in patients with ICC. Furthermore, patients with ICC with a high expression of TRAF4 and lymphatic metastasis were closely associated with a poorer prognosis compared with the other groups. Multivariate analysis indicated that the overexpression of TRAF4 was an independent prognostic indicator for patients with ICC. It was identified that a high level of TRAF4 facilitated the invasiveness of ICC cells via the activation of AKT signaling. The overexpression of TRAF4 may be a prognostic biomarker and candidate therapeutic target for patients with ICC.

[Indexed for MEDLINE]

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