Significance of ubiquitin-conjugating enzyme in esophageal cancer

目的：为了筛选关键分子以帮助预测乳腺癌的预后，我们先前进行并报道了基因表达谱分析：我们发现，在预后不良的患者中，泛素结合酶的RNA表达上调。因此，我们将重点放在泛素结合酶H10（UbcH 10），这是细胞周期从中期到后期的转变所不可缺少的，并通过评估更多患者的较长时间来研究食管癌病变中UbcH 10的蛋白表达水平是否影响食管鳞状细胞癌患者的预后。结果：UbcH 10在食管鳞癌及癌旁不典型增生组织中均有表达，而在正常组织中无表达。根据染色模式，患者根据表达进行分组：高（N=33）或低（N=88）。在淋巴管浸润、转移淋巴结数目、TNM分期、生存期等方面，高表达组的50%生存率为2.3年，而低表达组为9.9年（P<0.0001）。即使使用考克斯比例风险模型对0期至IV期进行多变量调整，属于高表达组的患者预后较差（HR：2.5; 95%CI：1.3-4.5;P=0.004）。

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.