自噬相关蛋白Beclin-1在ⅢB期结肠癌的表达及其与预后关系  

Expression of Beclin-1,an Autophagy-related Protein,in Stage ⅢB Colon Cancer and Its Relationship with Prognosis

作　　者：李宝秀[1] 李春燕[1] 彭瑞清[1] 王海英[1] 伍小军[1] 万德森[1] 张晓实[1] 

机构地区：[1]华南肿瘤学国家重点实验室中山大学肿瘤防治中心

出　　处：《中国肿瘤临床》2009年第3期146-149,共4页Chinese Journal of Clinical Oncology

基　　金：广东省自然科学基金(编号:05001693);广东省卫生厅科研基金资助(编号:B2007071)~~

摘　　要：目的：自噬是细胞利用溶酶体降解自身受损的细胞器和大分子物质的过程，是真核细胞的一种死亡形式。自噬在肿瘤发生发展中的作用尚不完全清楚。Beclin-1是一种双等位抑癌基因且是哺乳动物参与自噬的特异性基因。本研究观察肿瘤细胞自噬水平变化对ⅢB期结肠癌患者预后的影响。方法：收集我院1999年1月～2003年7月经过根治性手术治疗并有完整随访资料的115例ⅢB期结肠癌组织标本，用免疫组化方法观察自噬相关蛋白Beclin-1在癌组织与癌旁正常粘膜表达情况，分析beclin-1表达水平与患者临床病理参数关系及与患者预后的关系。结果：Beclin-1蛋白表达于肿瘤细胞膜、胞浆和（或）细胞核，正常粘膜缺乏Beclin—1表达。肿瘤组织Beclin—1阳性率达85．2％（98／115）；Beclin-1表达者的5年生存率较高（67.3％VS47．1％）。此外，Beclin-1表达与患者其它临床病理参数如年龄、性别、发病部位、病理类型、细胞分化程度及T分期无相关性。结论：局部晚期结肠癌细胞保留自噬功能没有提高肿瘤细胞的生存能力，而丧失自噬功能可能促进肿瘤进展。Objective： Autophagy is a form of eukaryotic cell death by which the cell recycles its components through self-consumption of cellular organelles and bulk cytoplasm using hydrolytic enzymes stored in lysosomes. The role of autophagy in carcinogenesis and tumor progression is elusive. Beclin-1, a key regulator of autophagy in mammals, has been considered a haploinsufficient tumor suppressor. This study investigates the expression of beclin-1 in stage Ⅲ B human colon cancer and analyzes the association of beclin-1 expression with clinocopathologic characteristics and prognosis. Methods： A total of 115 cases of colon cancer specimens were obtained from radically resected stage Ⅲ B colon cancer tumors between January 1999 and July 2003 with complete follow-up data in our center. Tissue arrays were constructed from formalin-fixed and paraffin-embedded tissues. The expression of beclin-1 in tumor tissue and adjacent normal tissue was examined with immunohistochemistry. The relationship between beclin-1 expression and clinicopathological parameters was analyzed. Results： Expression of beclin-1 was observed in the plasma membrane, cytoplasm and nucleus in tumor cells. In the tumor tissues analyzed, immunopositivity was observed for beclin-1 in 98 （85.2%） of the 115 tumor tissues. In contrast, adjacent non-cancerous tissues and normal tissues showed no or very weak expression of beclin-l. The 5-year overall survival rate for beclin-1 immunopositive cases was 67.3% and for beclin-1 immunonegative cases the rate was 47.1%. The 5-year overall survival rate was 68.9% for T3NoMo cases and 25.0% for T, NoM0 cases. There was a significant association of beclin-1 expression and T stage with 5-year overall survival rate. No significant correlation was found between beclin-1 expression and clinocopathologic characteristics including sex, age, tumor site,pathologic type, grade, and invasive depth （T stage）. Both univariate analysis and multivariate analysis showed that beclin-1 and T stage were independent prognost

关 键 词：自噬 BECLIN-1 结肠癌 预后 

分 类 号：R735.35[医药卫生—肿瘤] R329.2[医药卫生—临床医学]