乳腺癌组织CBL-B蛋白表达与生物学行为和预后关系  

Relationship of expression of CBL-Bprotein in breast cancer tissues with biological behaviour and its clinical prognosis

作　　者：邓淳 肖斌 李纬玮 陆景润 李林海 莫非 DENG Chun;XIAO Bin;LI Wei-wei;LU Jing-run;LI Lin-hai;MO Fei(Department of Basic Clinical Laboratory Medicine,School of Clinical Laboratory Science,Guizhou Medical University,Guiyang 550004,P.R.China;Department of Laboratory Medicine,General Hospital of Southern Theatre Command of PLA,Guizhou 510010,P.R.China;Clinical Laboratory Center of Affiliated Hospital of Guizhou Medical University,Guiyang 550004,P.R.China)

机构地区：[1]贵州医科大学医学检验学院临床检验学教研室,贵州贵阳550004 [2]中国人民解放军南部战区总医院检验科,广东广州510010 [3]贵州医科大学附属医院临床检验中心,贵州贵阳550004

出　　处：《中华肿瘤防治杂志》2020年第4期276-282,共7页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81802634);广东省自然科学基金(2018A030310014);军队后勤科研项目(CWH17C017);贵州省卫生计生委科学技术基金(gzwjkj2018-1-073).

摘　　要：目的Casitas B细胞淋巴瘤(Casitas B cell lymphoma,CBL)蛋白家族是一组具有环指结构域(really interesting new gene,RING)的E3泛素连接酶,CBL-B正是其中一员。本研究探讨CBL-B蛋白在乳腺癌组织中表达与预后的关系,为乳腺癌分子机制研究及改善患者预后提供帮助。方法免疫组化染色检测CBL-B在30例取自台州医院的乳腺癌组织和癌旁组织表达;通过构建过表达CBL-B的MDA-MB-231细胞株与正常的MDA-MB-231细胞株进行Transwell细胞迁移以及细胞侵袭实验;从USCS Xena数据库下载乳腺癌基因表达及临床信息等相关数据共1217例,通过生物信息学分析CBL-B对乳腺癌临床预后的作用。结果免疫组化实验结果显示,CBL-B在正常组织中得分(265.79±37.3)高于乳腺癌组织(205.39±27.6),t=25.67,P<0.001。Transwell迁移小室穿膜细胞数平均值,对照组与实验组分别为78±17、41±14,t=11.401,P=0.001;侵袭小室穿膜细胞数平均值,对照组与实验组分别为83±15、33±12,t=13.020,P=0.001;显示CBL-B蛋白对MDA-MB-231乳腺癌细胞迁移与侵袭能力均呈现抑制作用。在不同分子分型中,除HER2+亚型以外(t=0.689,P=0.481),CBL-B基因表达水平在Luminal A型(2.013±0.721,t=10.283,P=0.013)、Luminal B型(1.974±1.321,t=13.721,P=0.002)和基底样乳腺癌(2.152±1.220,t=12.321,P=0.005)中,均低于正常组织(2.321±0.317)。在不同浸润程度中,CBL-B基因表达水平(2.112±0.542)在混合型乳腺癌中最高,t=15.782,P=0.001;在黏液癌中(1.636±0.624)最低,t=14.212,P=0.001;生存曲线分析结果显示,CBL-B高表达的乳腺癌患者生存率较高,说明CBL-B与乳腺癌预后具有潜在的关联性,P<0.001。结论CBL-B表达水平与乳腺癌患者预后呈正关联,且在乳腺癌中呈现低表达的特点,预示它可能成为影响乳腺癌患者预后的一个新作用靶点。OBJECTIVE The E3 ubiquitin ligases CBL-Bis a member of Casitas B cell lymphoma(CBL)protein family that contain a single really interesting new gene(RING)domain.This study aimed to investigate the expression level of CBL-Bin breast cancer tissues and its relationship with clinical prognosis could provide help for the study of the molecular mechanism of breast cancer and to improve the prognosis of patients.METHODS The expression of CBL-Bin breast cancer tissues and adjacent tissues from breast cancer patients in Zhejiang Taizhou Hospital was detected by immunohistochemical staining.The ability of migration and invasion in CBL-B over-expressing MDA-MB-231 and normal MDA-MB-231 cell line were compared.The gene expression data and corresponding clinical information of 1217 breast cancer cases were downloaded from the USCS Xena database and the effects of CBL-Bon clinical prognosis of breast cancer were analyzed through bio-informatics.RESULTS The immunohistochemical results showed that the score of CBL-B in normal tissues(265.79±37.30)was higher than that in breast cancer(205.39±27.60),indicating that the expression of CBL-Bin normal tissues was higher than that in breast cancer tissues.The mean number of transwell transfused cells in the control group was 78±17 and the experimental group was 41±14(t=11.401,P=0.001),and the mean number of invasive-compartment trans-membrane cells in the control group was 83±15 and the experimental group was 33±12(t=13.020,P=0.001),suggesting that CBL-B protein could inhibit the migration and invasion of MDA-MB-231 cells.In different molecular subtypes,CBL-Bexpression level in Luminal Atype(FPKM=2.013±0.721,t=10.283,P=0.013),Luminal Btype(FPKM=1.974±1.321,t=13.721,P=0.002)and basal-like breast cancer(FPKM=2.152±1.220,t=12.321,P=0.005)was lower than that in normal tissues(FPKM=2.321±0.317)whereas in HER2+subtype(t=0.689,P=0.481),that is no significance difference.Among different infiltrate degrees,the expression of CBL-B was the highest in mixed breast cancer(FPKM=2.112±0.54

关 键 词：CBL-B 乳腺癌 分子分型 浸润程度 临床预后 

分 类 号：R737.9[医药卫生—肿瘤]