人肺腺癌干细胞的表型及其与肺腺癌患者预后的关系  

Lung adenocarcinoma stem cell phenotypes and their correlation with patient prognosis

作　　者：张雪艳[1] 郑必强[2] 韩宝惠[1] 黄进肃[1] 耿沁[2] 徐惠莉[2] 周瑾[2] 董强刚[2] 

机构地区：[1]上海交通大学附属胸科医院肺内科,200030 [2]上海交通大学肿瘤研究所肿瘤干细胞实验室

出　　处：《中华肿瘤杂志》2009年第11期836-840,共5页Chinese Journal of Oncology

基　　金：国家自然科学基金（30872952）;上海市科委纳米科技专项肇金（0852nm5800）;上海市科委肺癌早期诊断和技术研究课题（06DZ19501）;民政部十·五期间部级老年学研究项目（200847-2-06）

摘　　要：目的检测肺腺癌组织中肿瘤干细胞的表型，并分析其与肺腺癌患者预后的相关性。方法采用免疫荧光法检测57例肺腺癌组织肿瘤干细胞的3个表型标志，即表面活性蛋白C（SP-C）、细支气管非纤毛柱状细胞标志蛋白（CCSP）和OCT4。采用Cox多因素分析，评估检测结果与临床病理指标及患者生存之间的关系。结果57例肺腺癌组织均表达SP-C，其中52例可观察到CCSP^＋细胞，具有肺细支气管肺泡干细胞（BASC）的表型特征。52例SP-C^＋CCSP^＋绀织中，40例同时表达OCT4，进入OCT4^＋BASC组；12例不表达OCT4，进入OCTd—BASC组。统计分析的结果显示，肺腺癌干细胞的表型与肺腺癌的分化相关，OCT4^＋BASC表型多见于高中分化肿瘤，而OCT4^-BASC表型以低分化肿瘤为主。Cox多因素分析的结果显示，肺腺癌患者的生存与肿瘤的TNM分期及OCT4^＋BASC表型相关。结论肺腺癌干细胞具有BASC的表型特征（SP—C^＋CCSP^＋），此类肿瘤干细胞表达自我更新基因OCTd时，恶性程度高，患者的预后差。Objective To detect the cancer stem ceils and to evaluate their prognostic implication in patients with lung adenocarcinoma. Methods Three phenotypic markers of cancer stem cells （ SP-C, CCSP and OCT4 ） in lung adenocarcinoma were detected by immunofluorecence staining. The correlation among the clinicopathological parameters and phenotypes of cancer stem cells as well as survival were analyzed by Cox proportional hazard method. Results Of the 57 cases, cancer stem cells were detected in 52, including OCT4^＋ bronchioloalveolar stem cell （BASC） phenotype （ SP-C^＋ CCSP^＋ OCT4^＋ ） in 40 cases and OCT4^- BASC phenotype （SP-C^＋ CCSP^＋ OCT4^- ） in 12 cases. Statistical analysis revealed that the phenotype of cancer stem cells was related with the cellular differentiation, i.e. the OCT4^＋ BASC phenotype occurred more frequently in the well-differentiated tumors, while the OCT4 BASC phenotype usually presented in most of the poorly-differentiated ones. Cox analysis showed that the OCT4^＋ BASC phenotype was one of prognostic factors. Conclusion The lung adenocarcinoma stem cells have phenotypic features of bronchioalveolar stem cells （ SP-C^＋ CCSP^＋）. The expression of self-renewal regulatory gene OCT4 in these cells indicates an aggressive nature and unfavorable prognosis.

关 键 词：肺肿瘤 肿瘤干细胞 OCT4 预后 

分 类 号：R686[医药卫生—骨科学]