胃癌进展中转录因子e2f-1的表达变化及其意义

Change of Expression of Transcription Factor e2f-1 in Advancement of Gastric Cancer and Its Significances

目的研究转录因子e2f-1在胃癌发展过程中不同阶段的表达情况及其临床意义,判断其在胃癌发展中的作用。方法采用SABC免疫组化法检测121例胃癌原发灶中e2f-1的表达情况,分析其与临床病理特征和预后的关系。结果 121例患者e2f-1的表达阳性率为38.8%(47/121)。随着胃癌的进展,TNMⅠ～Ⅳ期e2f-1表达阳性率呈逐渐下降的趋势(r=-0.320,P<0.05):Ⅰa期62.5%(10/16),Ⅰb期47.1%(8/17),Ⅱ期55.0%(11/20),Ⅲa期40.0%(8/20),Ⅲb期27.3%(6/22),Ⅳ期15.4%(4/26);同时e2f-1的表达与肿瘤最大直径、浸润深度、淋巴结转移率和累及淋巴站亦呈负相关(P<0.05)。多参数检验分析显示组织学类型及生存期是e2f-1阳性表达的独立相关因素(P<0.05)。Log-Rank检验提示与术后生存相关的因素包括累及淋巴站、肿瘤最大直径、肿瘤位置、淋巴结转移率、浸润深度及TNM分期(P<0.05)。多因素Cox逐步回归分析提示累及淋巴站越远、e2f-1表达阳性率越高,则生存期越短(P<0.05)。TNM各期中:Ⅰ、Ⅱ期患者e2f-1的阳性高表达率与更短的生存期相关(r=-0.304,P<0.05),而且e2f-1呈阳性表达者其预后显著差于阴性表达者(χ2=13.437,P<0.05);而Ⅲ、Ⅳ期患者e2f-1的表达与生存期之间无统计学关系(P>0.05)。结论转录因子e2f-1是体现早期胃癌恶性行为的标记之一,表达阳性的早期患者生存时间显著缩短,是有效的预后判断因子;而在晚期胃癌中e2f-1表达降低,提示可能与其进展有关。

Objective To investigate the expression of transcription factor e2f-1 in the different development stages of gastric cancer,the relationships between clinicopathologic characteristics and e2f-1 expression status,as well as its influences on the prognosis.Methods The operative samples from primary lesion of 121 patients who underwent radical resection for gastric cancer were detected by SABC immunohistochemical staining.The relationships of e2f-1 expression with clinicopathologic characteristics and with the prognosis were observed by univariate,multivariate and relative analyses.Results The total positive expression rate of e2f-1 in all patients was 38.8%（47/121）.With the advancement of gastric cancer,the level of e2f-1 expression in TNMⅠ-Ⅳ stage was gradually decreased（r=-0.320,P〈0.05）：Ⅰa stage with 62.5%（10/16）,Ⅰb with 47.1%（8/17）,Ⅱwith 55.0%（11/20）,Ⅲa with 40.0%（8/20）,Ⅲb with 27.3%（6/22）,Ⅳ with 15.4%（4/26）.The expression of e2f-1 was significantly negative correlated with tumor diameter,depth of infiltration,lymph node metastasis ratio,and N stage（P〈0.05）.The multivariate analysis revealed that either histology type,or survival time was respectively an independent factor for e2f-1 expression（P〈0.05）.Log-Rank test showed the relative factors to survival included N stage,tumor diameter,tumor position,lymph node metastasis ratio,depth of infiltration,and TNM stage（P〈0.05）.Cox survival analysis found that both of later N stage and e2f-1 higher expression were independent prognostic factors（P〈0.05）.The higher e2f-1 expression was related to a poor survival in TNM stageⅠand Ⅱ patients（r=-0.304,P〈0.05）,the prognosis of patients with e2f-1 positive expression was worse than that of patients with negative expression（χ^2=13.437,P〈0.05）,and there was no statistic relationship between the expression of e2f-1 and prognosis in stage Ⅲ and Ⅳ patients（P〉0.05）.Conclusions e2f-1,as a useful marker,seems to be an indication for the malignant behavior in relatively earlier gastric cancer,in which the e2f-1 positive expression shares a significantly poor survival.And the lower expression of e2f-1 has been identified in later advanced gastric cancer,the more malignances in advanced gastric cancer might associate with a lower expression of e2f-1.