Expression and clinical significance of cullin 4A in cholangiocarcinoma

Abstract

Objective To explore the expression of cullin 4A (CUL4A) in cholangiocarcinoma tissues and its clinical significance. Methods Primary fresh cholangiocarcinoma tissues (n=35) and normal bile duct tissues (n=15) from patients who underwent curative surgery in Binzhou People′s Hospital of Shandong Province from February 2011 to December 2013 were collected. The expressions of CUL4A mRNA were detected by quantitative real-time PCR (qRT-PCR). Then, cholangiocarcinoma tissues (n=72) and normal bile duct tissues (n=36) from patients who underwent curative surgery in Binzhou People′s Hospital of Shandong Province from January 2008 to January 2014 were collected. The expressions of CUL4A protein were tested by immunohistochemistry. The relationships between the expression of CUL4A and the patients′ clinicopathologic features and prognosis were analyzed. Results The expression of CUL4A mRNA in cholangiocarcinoma tissues was obviously higher than that in normal bile duct tissues (3.876±0.975 vs. 1.216±0.265), and the diffe-rence was statistically significant (t=12.23, P<0.001). The positive rates of CUL4A protein in cholangiocarcinoma and normal bile duct tissues were 70.8% (51/72) and 2.8% (1/36) respectively, and the diffe-rence was statistically significant (χ2=44.524, P<0.001). The expression of CUL4A protein in cholangiocarcinoma was related to the differentiated degree (χ2=4.341, P=0.037), neural invasion (χ2=8.326, P=0.004), TNM stage (χ2=7.745, P=0.005), lymph node metastasis (χ2=3.869, P=0.049) and vascular invasion (χ2=5.555, P=0.018). Survival analysis results showed that the median survival time of CUL4A positive patients was significantly shorter than that of CUL4A negative patients (32.40 months vs. 51.30 months), and the difference was statistically significant (χ2=6.561, P=0.011). Conclusion The expression of CUL4A in cholangiocarcinoma tissues is higher than that in normal bile tissues. CUL4A plays an important role in the process of tumor invasion and metastasis and indicates poor prognosis, which may become a potential target for the diagnosis and therapy of the cholangiocarcinoma. Key words: Bile duct neoplasms; Immunohistochemistry; Cullin 4A