长链非编码RNA母系表达基因3在垂体生长激素细胞肿瘤组织中的表达及其临床病理相关性分析  

Expression and clinicopathological correlation of long non-coding RNA MEG3 in GH-PitNETs

作　　者：董伟[1] 陈一元 李振业[2] 张亚卓[2] 董晓柳[3] 张欢[1] 高华[2] Dong Wei;Chen Yiyuan;Li Zhenye;Zhang Yazhuo;Dong Xiaoliu;Zhang Huan;Gao Hua(Department of Neurosurgery,Tangshan People's Hospital,Tangshan 063001,China;Beijing Institute of Neurosurgery,Capital Medical University,Bejing 100070,China;Department of Neurology,Tangshan People's Hospital,Tangshan 063001,China)

机构地区：[1]唐山市人民医院神经外科,唐山063001 [2]首都医科大学,北京市神经外科研究所,北京100070 [3]唐山市人民医院神经内科,唐山063001

出　　处：《中华神经外科杂志》2024年第11期1154-1159,共6页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金(82103048);中央引导地方科技发展资金(22627704G);河北省自然科学基金精准医学联合基金细化项目(H2020105017,H2022105014);唐山市人才项目(202203026)。

摘　　要：目的探讨长链非编码RNA(LncRNA)母系表达基因3(MEG3)在垂体生长激素(GH)细胞肿瘤组织中的表达水平及其临床病理相关性。方法利用ChipBase v3.0数据库分析正常垂体组织中MEG3与谱系分化因子核受体亚家族5 A族成员1(NR5A1)、POU1类同源盒1(POU1F1)、T-box转录因子19(TBX19)、GH、GH受体(GHR)、GH释放激素受体(GHRHR)、胰岛素样生长因子1受体(IGF1R)、生长抑素受体2/5(SSTR 2/5)基因的相关性。选取来源于唐山市人民医院神经外科的28例垂体GH细胞肿瘤患者的手术切除肿瘤标本, 采用实时定量PCR法检测肿瘤组织中MEG3的表达水平, 采用免疫组织化学染色方法检测肿瘤组织中GH、GHRHR和SSTR 5蛋白的表达情况。采用Pearson相关性检验分析肿瘤标本中MEG3基因表达水平与GH、GHRHR和SSTR 5蛋白表达水平的关系。根据MEG3基因表达水平, 将患者分为MEG3高表达组(表达水平≥0.14, 14例)和低表达组(表达水平<0.14, 14例), 分析MEG3基因表达水平与患者的临床病理特征的相关性。结果 ChipBase v3.0数据库分析结果显示, 31种器官中, 垂体的MEG3表达水平与POU1F1、NR5A1和TBX19表达水平的相关性分别排名第1(r=0.60)、9(r=0.32)和29位(r=0.28)(均P<0.05)。31种器官的MEG3基因表达水平与GH、GHRHR和SSTR 5基因表达水平的相关性中, 垂体均位居第1(r值分别为0.60、0.72和0.57)(均P<0.05);MEG3表达水平与IGF1R和GHR表达水平的相关性中, 垂体分别位居第4(r=0.74)、18位(r=0.28)(均P<0.05);而与SSTR 2表达水平的相关性无统计学意义(P>0.05)。Pearson相关分析结果显示, MEG3基因表达水平与肿瘤组织标本中GH、GHRHR和SSTR 5蛋白的免疫组织化学评分均呈正相关(r值分别为0.59、0.65和0.47, 均P<0.05)。MEG3高表达组与低表达组患者的肿瘤体积和最大径的差异均无统计学意义(均P>0.05)。MEG3高表达组和低表达组的Ki-67增殖指数[M(Q1, Q3)]分别为2.0%(1.5%, 2.6%)和3.0%(2.0%, 6.6%), 差异�Objective To investigate the expression levels of long non-coding RNA(LncRNA)Maternally Expressed Gene 3(MEG3)in Growth Hormone(GH)cell adenoma tissues and its clinical and pathological correlation.Methods The ChipBase v3.O database was utilized to analyze the correlation between MEG3 expression in normal pituitary tissues and lineage differentiation factors such as Nuclear Receptor Subfamily 5 Group A Member 1(NR5A1),POU Class 1 Homeobox 1(POUIF1),T-Box Transcription Factor 19(TBX19),CH,Growth Hormone Receptor(GHR),Growth Hormone Releasing Hormone Receptor(GHRHR),Insulin Like Growth Factor 1 Receptor(IGF1R),and Somatostatin Receptor 2/5(SSTR2/5).Tumor samples were obtained from 28 patients with GH cell adenomas at the Neurosurgery Department of Tangshan People's Hospital.MEG3 levels in the tumor tissues were detected using RT-qPCR.Immunohistochemistry staining was used to assess the expression levels of GH,GHRHR,and SSTR 5 in tumor tissues.Pearson correlation analysis was conducted to evaluate the relationship between MEG3 gene levels and the expression levels of GH,GHRHR,and SSTR 5 in the tumor samples.Based on MEC3 gene expression levels,patients were divided into two groups:the high expression group(expression level≥0.14,14 cases)and the low expression group(expression level<0.14,14 cases).The correlation between MEG3 gene expression levels and the clinical pathological characteristics of the patients was analyzed.Results Among the 31 organs,pituitary gland was ranked 1st(r=0.60),9th(r=0.32)and 29th(r=0.28)in the correlation relationship of MEC3 with POU1F1,NR5A1 and TBX19,respectively(all P<0.05).The pituitary gland were all ranked first in terms of the correlation relationship of GH(r=0.60),GHRHR(r=0.72)and SSTR 5(r=0.57),and 4th in IGF1R(r=0.74),18th in GHR(r=0.28)(all P<0.05),and no correlation in SSTR 2(P>0.05).Pearson correlation analysis showed that the MEG 3 level was positively correlated with the immunohistochemistry scores of CH,GHRHR and SSTR 5 in the specimens(r=0.59,0.65,0.47,respectively).The

关 键 词：垂体肿瘤 生长激素 RNA 长链非编码 母系表达基因3 细胞增殖 肿瘤分化 

分 类 号：R736.4[医药卫生—肿瘤]