雌激素受体阳性乳癌lncRNA的差异性表达研究  

DIFFERENTIAL EXPRESSION OF LONG NON-CODING RNAS IN ESTROGEN RECEPTOR-POSITIVE BREAST CANCER

作　　者：弭苗苗 姜慧慧 魏晓楠 刘杰[1] 辛钰 孙成铭[1] MI Miaomiao;JIANG Huihui;WEI Xiaonan;LIU Jie;XIN Yu;SUN Chengming(Center for Laboratory Diagnosis,Yantai Yuhuangding Hospital Affiliated to Qingdao University,Yantai 264000,China)

机构地区：[1]青岛大学附属烟台毓璜顶医院检验中心,山东烟台264000 [2]青岛市妇女儿童医院

出　　处：《青岛大学学报（医学版）》2021年第3期333-338,共6页Journal of Qingdao University(Medical Sciences)

基　　金：山东省重大科技创新工程项目(2019JZZY01-1018);烟台市科技计划项目(2019MSGY133)。

摘　　要：目的基于生物信息学技术,筛选与雌激素受体(ER)阳性乳癌相关的长链非编码RNA(lncRNA),并初步探讨其与病人预后的关系。方法通过基因芯片技术,对4对手术切除的ER阳性乳癌组织及其癌旁正常组织进行lncRNA和mRNA的表达谱分析,并对差异表达的mRNA进行GO功能注释、KEGG通路富集分析及疾病富集分析;应用qRT-PCR方法对差异表达的lncRNA在40对ER阳性乳癌组织及癌旁组织中进行验证,同时在ER阳性乳癌细胞株MCF-7及正常乳腺上皮细胞MCF-10A做进一步验证;最后通过TCGA数据库对lncRNA在ER阳性乳癌组织中的表达水平进行分组,使用Kaplan-Meier生存曲线分析其表达量与预后的关系。结果基因芯片技术分析显示,在ER阳性乳癌组织及其癌旁正常组织共筛选出具有差异性表达的mRNA 3 949个、lncRNA 4 050个。选取其中差异表达最显著的7个lncRNA在组织中做进一步验证,发现LINC01614(t=10.380,P<0.01)、AC044784.1(t=3.490,P<0.01)、CTD-2510F5.4(t=3.235,P<0.01)在乳癌组织高表达;细胞学验证结果显示,LINC01614(t=3.714,P<0.05)、AC044784.1(t=5.827,P<0.01)、CTD-2510F5.4(t=4.415,P<0.05)在乳癌细胞株中同样高表达。TCGA数据库预后分析显示,纳入的791例ER阳性乳癌病人中,LINC01614高表达者预后相对更差(χ^(2)=7.50,P<0.01)。结论 LINC01614在ER阳性乳癌中高表达可能与乳癌的发生、发展及预后相关,可能成为乳癌治疗新的作用靶点。Objective To screen out the long non-coding RNAs(lncRNAs)associated with estrogen receptor(ER)-positive breast cancer based on bioinformatics technology,and to investigate their association with patient prognosis.Methods The gene microarray technique was used to analyze the expression profiles of lncRNAs and mRNAs in four pairs of surgically resected ER-positive breast cancer tissue samples and adjacent tissue samples,and GO functional annotation,KEGG pathway enrichment analysis,and disease enrichment analysis were performed for differentially expressed mRNAs.The qRT-PCR method was used to verify the differentially expressed lncRNAs in 40 pairs of ER-positive breast cancer tissue samples and adjacent tissue samples,and further verification was performed in the ER-positive breast cancer cell line MCF-7 and the normal breast epithelial cell line MCF-10A.The Cancer Genome Atlas(TCGA)database was used for grouping based on the expression level of lncRNAs in ER-positive breast cancer tissue,and the Kaplan-Meier survival curve was used to investigate the association of expression level with prognosis.Results The gene microarray analysis showed that a total of 3949 differentially expressed mRNAs and 4050 differentially expressed lncRNAs were screened out between ER-positive breast cancer tissue and adjacent tissue.Further verification of the 7 lncRNAs with strongest differential expression showed that LINC01614(t=10.380,P<0.01),AC044784.1(t=3.490,P<0.01),and CTD-2510F5.4(t=3.235,P<0.01)were highly expressed in breast cancer tissue,and cytological verification showed that LINC01614(t=3.714,P<0.05),AC044784.1(t=5.827,P<0.01),and CTD-2510F5.4(t=4.415,P<0.05)were also highly expressed in the breast cancer cell line.The prognostic analysis based on TCGA database showed that among the 791 patients with ER-positive breast cancer,there was significant difference in the patients with high expression of LINC01614 tended to have poor prognosis(χ^(2)=7.50,P<0.01).Conclusion High expression of LINC01614 in ER-positive breast cancer

关 键 词：乳房肿瘤 RNA 长链非编码 寡核苷酸序列分析 计算生物学 受体 雌激素 预后 

分 类 号：R737.9[医药卫生—肿瘤] R394-33[医药卫生—临床医学]