单泛素化组蛋白H2B在食管癌中的表达及其临床意义

Expression of monoubiquitination histone H2B in esophageal carcinoma and its clinical significance

目的探讨单泛素化组蛋白H2B(H2Bub)在食管癌组织中的表达及其与预后的相关性。方法选取2010年5月至2015年12月在山西省肿瘤医院行胸段食管癌根治术的患者75例,用免疫组织化学法检测食管癌及癌旁组织H2Bub蛋白的表达水平。分析H2Bub表达水平与患者临床病理特征的关系,采用Kaplan-Meier法分析H2Bub表达水平与生存的关系。结果食管癌及癌旁组织中H2Bub蛋白均阳性表达,但癌组织中无弱阳性表达者,癌旁组织中有弱阳性表达者;癌组织H2Bub强阳性表达率为84.0%(63/75),高于癌旁组织的22.7%(17/75)(χ^(2)=34.68,P<0.001)。同癌旁组织相比,癌组织中64.0%(48/75)H2Bub表达上调,2.7%(2/75)表达下调。癌组织H2Bub较癌旁组织表达上调与患者性别、年龄、肿瘤长径、淋巴结是否转移、T分期均无关(均P>0.05),而低分化癌组织中H2Bub表达上调患者比例低于中分化和高分化癌组织[43.8%(7/16)比66.7%(34/51)、87.5%(7/8),P=0.037]。H2Bub中等阳性(12例)和强阳性(63例)表达的食管癌患者中位总生存时间分别为70个月(95%CI 45~95个月)、68个月(95%CI 54~82个月),差异无统计学意义(P=0.606);癌组织H2Bub表达较癌旁组织上调的48例患者中,食管癌低分化组(7例)中位总生存时间短于高分化组(7例)及中分化组(34例)[36个月(95%CI 24~37个月)比68个月(95%CI 38~98个月)、68个月(95%CI 44~91个月)],差异均有统计学意义(均P<0.05)。结论与癌旁组织相比,食管癌组织中H2Bub表达水平上调;低分化食管癌患者H2Bub表达水平上调明显,且预后差。

Objective To investigate the expression of monoubiquitination histone H2B(H2Bub)in esophageal cancer tissues and its correlation with the prognosis of patients.Methods A total of 75 patients who underwent thoracic esophagectomy in Shanxi Province Cancer Hospital from May 2010 to December 2015 were selected.The expression of H2Bub protein in esophageal carcinoma and para-carcinoma tissues was detected by using immunohistochemical method.The relationship between H2Bub expression level and the clinicopathological characteristics was analyzed,Kaplan-Meier method was used to analyze the relationship H2Bub expression level and the survival.Results H2Bub was positively expressed in esophageal carcinoma and para-carcinoma tissues,and weakly positive expressed H2Bub was found in para-carcinoma tissues,while not found in esophageal carcinoma tissues.The strongly positive expression rate of H2Bub in esophageal carcinoma tissues was higher than that in para-carcinoma tissues[84.0%(63/75)vs.22.7%(17/75),χ^(2)=34.68,P<0.001].Compared with para-carcinoma tissues,64.0%(48/75)of H2Bub expression level in carcinoma tissues was up-regulated,and 2.7%(2/75)of H2Bub expression level was down-regulated.The up-regulated expression of H2Bub in esophageal carcinoma tissues compared with para-carcinoma tissues was not related with the gender,age,tumor diameter,lymph node metastasis and T staging(all P>0.05).The proportion of patients with up-regulated expression of H2Bub in poorly differentiated carcinoma tissues was lower than that in moderately and highly differentiated carcinoma tissues[43.8%(7/16)vs.66.7%(34/51),87.5%(7/8),P=0.037].The median overall survival time was 70 months(95%CI 45-95 months)and 68 months(95%CI 54-82 months),respectively in 12 esophageal carcinoma patients with moderately positive expressed H2Bub and 63 esophageal carcinoma patients with strongly positive expressed H2Bub,and the difference was statistically significant(P=0.606).Among 48 patients with up-regulated expression of H2Bub in esophageal carcinoma tissues compared with para-carcinoma tissues,the median overall survival time of poorly differentiated esophageal carcinoma group(7 cases)was shorter than that of highly differentiated(7 cases)and moderately differentiated(34 cases)esophageal carcinoma group[36 months(95%CI 24-37 months)vs.68 months(95%CI 38-98 months),68 months(95%CI 44-91 months)],and the differences were statistically significant(all P<0.05).Conclusions The expression level of H2Bub in esophageal carcinoma tissues is up-regulated compared with that in para-carcinoma tissues.The up-regulated H2Bub expression level of patients with poorly differentiated esophageal carcinoma with poor prognosis is obvious.