摘要
目的 Ki-67是目前应用最广泛的细胞增殖标志之一,而B细胞淋巴瘤-6(B-cell lymphoma-6,Bcl-6)基因本身具有不稳定性,其在淋巴瘤预后中是否能作为判断标记还需进一步研究。本研究主要探讨B细胞非霍奇金淋巴瘤(B-non Hodgkin lymphoma,B-NHL)组织、氢醌诱变的TK6淋巴母细胞及其裸鼠荷瘤体中原癌基因Bcl-6和增殖细胞核抗原Ki-67的表达情况及两者间的相关性。方法采用免疫组化GTVisionTM二步法对东莞东华医院2014-01-01-2018-12-31收治的85例B-NHL组织切片、氢醌诱变的人TK6淋巴母细胞及其裸鼠荷瘤体中Ki-67和Bcl-6表达情况进行检测;运用Spearman相关性分析及χ2检验分析2个基因的表达相关性及在临床分型诊断中的意义;荧光定量聚合酶链反应法检测氢醌诱导的TK6细胞中Bcl-6和Ki-67基因的表达。结果 85例B-NHL组织中,Ki-67高表达率为82.35%(70/85),Bcl-6阳性率为84.71%(72/85)。Ki-67在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中高表达率为95.35%(41/43),有别于非DLBCL中的69.05%(29/42),χ^2=10.113,P=0.001;Ki-67表达和B-NHL的恶性程度差异有统计学意义的关联(χ^2=21.642,P<0.001),并与Bcl-6在B-NHL组织中的表达呈正相关,r=0.403,P<0.001;但与年龄、性别均无关联,P>0.05;≥45岁患者Bcl-6阳性率高于<45岁患者(χ^2=9.939,P<0.05),说明Bcl-6的表达与年龄有关,而与性别、病理类型和恶性程度均无关联(P>0.05),氢醌诱导恶变的TK6细胞中Ki-67的mRNA表达上升(t=3.853,P=0.031),且诱变细胞的裸鼠荷瘤实验瘤体经免疫组化检测可见Ki-67强阳性(均值为80%)和Bcl-6的阳性(均值为11.5%)。结论 Ki-67高表达是DLBCL的重要判别指标,且与B-NHL的恶性程度有关;氢醌暴露可能引起B-NHL疾病通路中相关癌基因Ki-67和Bcl-6的表达改变,且二者在蛋白水平具有潜在的相关性。
OBJECTIVE Ki-67 is one of the most widely used cell proliferation markers nowadays and the genetic instablity of B-cell lymophoma-6(Bcl-6)itself suggest their usage as markers in the prognosis of lymphoma,but which still needs further study.This study aimed to investigate the expression of Ki-67 and Bcl-6,and their relationship in B non-Hodgkin lymphoma(B-NHL)tissues,hydroquinone(HQ) malignant transformed TK6 lymphoblastoid cells(HQ-MT-TK6)and its corresponding xenografts from nude mice.METHODS GTVisionTM immunohistochemistry(IHC)was used to detect the expressions of Ki-67 and Bcl-6 in 85 B-NHL tissues diagnosed in Dongguan Tungwah Hospital from 1/1/2014 to 12/31/2018.Spearman correlation analysis andχ^2 test were used to analyze their correlation and their relationship with clinical characteristics.Quantitative real-time PCR was applied to measure the expressions of Ki-67 and Bcl-6 in HQ-MT-TK6 cells and corresponding xenografts from nude mice.RESULTS The higher expression of Ki-67 in 85 B-NHL tissues was 82.35%(70/85),and the expression of Bcl-6 was 84.71%(72/85).The proportion of higher expression of Ki-67 in Diffuse large B cell lymphoma(DLBCL)was 95.35%(41/43),which was different with the69.05%(29/42)of non-DLBCL (χ^2=10.113,P=0.001),meanwhile,the higher expression of Ki-67 was associated with the malignant degree of B-NHL (χ^2=21.642,P<0.001).The expression of Ki-67 was related to that of Bcl-6 in B-NHL tissues(r=0.403,P<0.001).The mRNA of Ki-67 was increased in TK6 malignant transformed cells(t=3.853,P=0.031),whose corresponding xenografts of nude mice displayed higher expression of Ki-67(mean 80%)and positive expression of Bcl-6(mean 11.5%)by IHC.CONCLUSION The expression of Ki-67 might be an important indicator for DLBCL diagnosis,and is associated with the malignant degree of B-NHL;HQ exposure might cause the variant of protein expression of both Ki-67 and Bcl-6 in B-NHL.
作者
李良
潘志杰
张海桥
凌晓璇
黄锦叶
钟柏森
李洁优
刘林华
LI Liang;PAN Zhi-jie;ZHANG Hai-qiao;LING Xiao-xuan;HUANG Jin-ye;ZHONG Bai-sen;LI Jie-you;LIU Lin-hua(Department of Pathology,Dongguan Tungwah Hospital,Dongguan 523110,P.R.China;School of Public Health,Guangdong Medicol University,Dongguan 523808,P.R,China;Key Laboratory of Environmental Medicine of Dongguan City,Guangdorig Medical University,Dongguan 523808,P.R.China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2020年第13期1064-1069,共6页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(81202231)
广东省自然科学基金面上项目(2018A0303130240)
广东省医学科研基金(A2018225)
广东省教育厅青年创新人才项目(2014KQNCX102)
广东省科技计划(2013B021800069)
广东省大学生科技创新培育专项资金(pdjh2016a0212)
广东医科大学国家级和省级大学生创新创业训练计划(201410571059,20151057855)
广东医科大学博士启动(B201721,B2019027)。
