High expression of TOP2A gene predicted poor prognosis of hepatocellular carcinoma after radical hepatectomy

Hongyu Cai, Xinhua Zhu, Fei Qian, Bingfeng Shao, Yuan Zhou, Yixin Zhang, Zhong Chen


Background: Topoisomerase (DNA) II alpha (TOP2A) is the up-regulated gene of the chromosome aggregation pathway. This gene encodes DNA topoisomerase, which can control and change the topological state of DNA during transcription and replication, participate in chromosome agglutination, separation, and relieve stress from kinking. Abnormally high expression of TOP2A is often associated with active cell proliferation. In studies of breast cancer, endometrial cancer, and adrenal cancer, it was found that high expression of TOP2A suggested a poor prognosis.
Methods: A total of 15 pairs of fresh hepatocellular carcinoma (HCC) specimens and adjacent tissues were assembled, and the difference of TOP2A mRNA and protein expression level between tumor and adjacent tissues was detected by RT-PCR and Western blotting analysis, respectively. A total of 84 HCC paraffin specimens were selected for routine pathological grading. TOP2A expression was detected by immunohistochemistry (IHC). The correlation between TOP2A expression and clinicopathological features and survival time was analyzed.
Results: The expression of TOP2A mRNA and protein in HCC tumor tissues was significantly higher than that in the adjacent tissues. IHC results indicated that the TOP2A positive rate in tumor tissues was significantly higher than that in adjacent tissues (84.52%, 71/84 vs. 8.33%, 7/84). High TOP2A expression was associated with poor tumor differentiation, significant cirrhosis, and larger tumor diameter. Among the patients whose survival time exceeded 60 m, 14 patients (37.84%, 14/37) had a high expression of TOP2A. Among the patients whose survival time was less than 60 m, the TOP2A expression was high in 37 cases (78.72%, 37/47). Kaplan-Meier survival analysis showed that the survival time of the group with low or no TOP2A expression was better than that of the group with high TOP2A expression (P=0.0011). Regression analysis of the clinical characteristics and 5-year survival follow-up data of 84 patients showed that cirrhosis and TOP2A high expression were the independent factors influencing the prognosis of HCC, while gender, age, tumor grade, hepatitis B virus (HBV) infection, and tumor size did not affect 5-year survival.
Conclusions: The high expression of TOP2A is associated with the invasiveness and poor prognosis of HCC tumors, and, together with liver cirrhosis, can be a prognostic indicator of radical HCC resection.