Chen Shi-Feng, Gong Chang, Luo Ming, Yao He-Rui, Zeng Yun-Jie, Su Feng-Xi
Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P. R. China.
Chin J Cancer. 2011 Sep;30(9):638-44. doi: 10.5732/cjc.011.10084.
Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in tumorigenesis. Whether Ubc9 is involved in the chemoresistance of breast cancer remains unknown. In this study, we aimed to evaluate the contribution of Ubc9 in the chemoresistance of breast cancer. Immunohistochemistry (IHC) was used to examine the expression level of Ubc9. Chi-square test, Wilcoxon test, and one-way ANOVA were applied to analyze the relationship between Ubc9 expression, clinicopathologic features, and clinical response to neoadjuvant chemotherapy. The significance of variables for survival was analyzed by the Cox proportional hazards model in a multivariate analysis. Kaplan-Meier survival curves were plotted and log-rank test was performed. The proportion of Ubc9-positive cells was higher in invasive ductal carcinoma than in normal breast tissues [(48.48 ± 17.94)% vs. (5.82 ± 2.80)%, P < 0.001]. High Ubc9 expression was associated with poor differentiation (Χ² = 6.538, P = 0.038), larger tumor size (Χ² = 4.701, P = 0.030), advanced clinical stage (Χ² = 4.651, P = 0.031), lymph node metastasis (Χ² = 9.913, P = 0.010), basal-like phenotype (Χ² = 8.660, P = 0.034), and poor clinical response to neoadjuvant chemotherapy (Χ² = 11.09, P = 0.001). The expected 6-year cumulative disease-free survival rate was 87.32% in patients with low Ubc9 expression compared to 68.78% in those with high Ubc9 expression (Χ² = 4.289, P = 0.038). These data indicate that high Ubc9 expression correlates with poor response to chemotherapy and poor clinical prognosis.
泛素结合酶9(Ubc9)是唯一参与类泛素化修饰的结合酶,可调节蛋白质功能,并在肿瘤发生过程中发挥重要作用。Ubc9是否参与乳腺癌的化疗耐药性尚不清楚。在本研究中,我们旨在评估Ubc9在乳腺癌化疗耐药性中的作用。采用免疫组织化学(IHC)检测Ubc9的表达水平。应用卡方检验、Wilcoxon检验和单因素方差分析来分析Ubc9表达、临床病理特征与新辅助化疗临床反应之间的关系。通过Cox比例风险模型在多因素分析中分析生存变量的意义。绘制Kaplan-Meier生存曲线并进行对数秩检验。浸润性导管癌中Ubc9阳性细胞的比例高于正常乳腺组织[(48.48±17.94)%对(5.82±2.80)%,P<0.001]。Ubc9高表达与低分化(Χ²=6.538,P=0.038)、肿瘤体积较大(Χ²=4.701,P=0.030)、临床分期较晚(Χ²=4.651,P=0.031)、淋巴结转移(Χ²=9.913,P=0.010)、基底样表型(Χ²=8.660,P=0.034)以及新辅助化疗临床反应较差(Χ²=11.09,P=0.001)相关。Ubc9低表达患者的预期6年无病累积生存率为87.32%,而Ubc9高表达患者为68.78%(Χ²=4.289,P=0.038)。这些数据表明,Ubc9高表达与化疗反应差和临床预后不良相关。