GSK-3β在胃肠胰神经内分泌肿瘤中的表达及其对预后的影响

Expression of GSK-3β in gastroenteropancreatic neuroendocrine neoplasms and its effect on prognosis

目的探讨糖原合成酶激酶-3β(GSK-3β)在胃肠胰神经内分泌肿瘤患者(GEP-NENs)组织中的表达及其与临床病理特征和预后的关系。方法收集西安交通大学第一附属医院2010年1月~2017年12月经病理诊断为GEP-NENs的69例患者临床资料,免疫组化检测GSK-3β在GEP-NENs组织中的表达,同时选取10例GEP-NENs的正常组织(取自癌旁10cm以外)为对照组,并分析GSK-3β与患者临床病理特征和预后的关系。结果 69例GEP-NENs患者组织中,GSK-3β的表达显著高于正常组织(P=0.006)。晚期(Ⅲ+Ⅳ期)患者的GSK-3β表达强度高于Ⅰ+Ⅱ期(P=0.020);GSK-3β在G3患者中的表达明显高于G1+G2患者(P=0.001);有淋巴结转移的GEP-NENs患者组织中GSK-3β表达强度高于无淋巴结转移患者(P=0.022)。69例GEP-NENs患者mOS为45个月,总生存率为66.7%。其中,GSK-3β低中表达者(37例,53.6%,未达到)的预后明显优于GSK-3β高表达者(32例,46.4%,24.7个月)(P=0.013)。GSK-3β低中表达者中,G1+G2者(27例,73%,未达到)的预后明显优于G3者(10例,27%,35个月)(P=0.004)。结论 GSK-3β在GEP-NENs组织中过表达;病理分级对GSK-3β低中表达患者的预后有预测作用。

Objective To explore the expression of glycogen synthase kinase-3(GSK-3β) in gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) and its relationship with clinicopathological characteristics and prognosis. Methods 69 patients diagnosed as GEP-NENs from January, 2010 to December, 2017 were selected from the First Affiliate Hospital of Xi’an Jiaotong University for this study. 69 GEP-NENs’ tissues were collected and the expression level of GSK-3β was evaluated by immunohistochemistry, with 10 normal tissues served as control. A statistical analysis was performed by using SPSS 21.0. The relationship between clinicopathological characteristics and patients’ survival were investigated by K-M survival analysis and Cox regression analysis. Results GSK-3β was significantly igher expressed in the 69 tumor tissues tested than that of in control group(P=0.006). The expression of GSK-3β in patients with stage Ⅲ+Ⅳ was higher than that of stage Ⅰ+Ⅱ(P=0.020);the expression level of GSK-3β in patients with G1+G2 was lower than that of G3(P=0.001). The expression level of GSK-3β in patients without lymphatic metastasis was also lower than that of those with lymphatic metastasis(P=0.022). For 69 patients with GEP-NENs, overall survival was 66.7%. Median overall survival was 45 months. For survival analysis, the patients’ survival distribution with weak-positive and positive expression of GSK-3β(37 cases, 53.6%, unreached) was better than those with strong-positive expression of GSK-3β(32 case, 46.4%, 24.7 month)(P=0.013). Among the patients of weak-positive and positive expression of GSK-3β, only those with G1 + G2(27 cases, 73%, unreached) showed superior survival than those with G3(10 cases, 27%, 35 months)(P=0.004). Conclusion The overexpression of GSK-3β in GEP-NENs tumor tissues indicated poor survival. Grade could predict prognosis in the patients of weak-positive and positive GSK-3β expression.