Significance of ubiquitin-conjugating enzyme in esophageal cancer

目的：为了筛选关键分子以辅助预测食道癌的预后，我们先前开展并报道了基因表达谱：我们发现，在预后较差的患者中，泛素结合酶的RNA表达上调。因此，我们聚焦于细胞周期从中期到后期过渡所必需的泛素结合酶H10(UbcH10)，通过对更多的患者进行更长时间的评估，来研究UbcH10在食管癌病变中的表达水平是否影响食管鳞癌患者的预后。实验设计：对121例食管鳞癌石蜡包埋组织标本进行抗UbcH10抗体免疫组织化学染色。根据染色模式，患者按表达情况分组：高表达(N=33)或低表达(N=88)。在淋巴管侵袭、转移淋巴结数目、TNM分期和生存率方面，高表达组的50%生存率为2.3年，而低表达组为9.9年(P&lt；0.0001)。即使使用COX比例风险模型对0期至IV期进行多因素调整，高表达组患者的预后也较差(HR：2.5；95%CI：1.3~4.5；P=0.004)。结论：UbcH10蛋白高表达可能是食管鳞癌新的不良预后因素。

Purpose : To screen key molecules to aid the prediction of prognosis in esophagealcancer, we previously carried out and reported gene-expression profiling : we found that RNA expressions of ubiquitin-conjugating enzymes were upregulated in patients with a poor outcome. Therefore, we focused on ubiquitin-conjugating enzyme H10 (UbcH10) which is indispensable the cell-cycle transition from metaphase to anaphase, and investigated whether this protein expression levels of UbcH10 in cancerous esophageal lesions affected the prognosis of patients with esophageal squamous cell carcinoma by evaluating more patients for a longer period.Experimental Design : Paraffin-embedded tissue samples from 121 patients with esophageal squamous cell carcinoma were stained with anti-UbcH10 antibody for immunohistochemical analysis.Results : UbcH10 was expressed in cancerous and dysplastic lesions, but not in normal tissue. Depending on the staining pattern, patients were grouped according to expression : high (N=33) or low (N=88). There were significant differences between the groups in terms of invasion into lymphatic vessels, number of metastatic lymph nodes, TNM classification, and stages as well as survival: the 50% survival rate in the high expression group was 2.3 years, as compared with 9.9 years for the low expression group (P<0.0001). Even with multi-variate adjusting for stage 0 to stage IV using the Cox proportional hazard model, patients belonging to the high-expression group had a poorer prognosis (HR:2.5;95% Cl:1.3-4.5;P=0.004).Conclusions : High UbcH10 protein expression seems to be a novel poor prognosis in esophageal squamous cell carcinoma.