基于公共数据库分析NPY1R在乳腺癌中的表达及与他莫昔芬耐药的关系  

Analysis of NPY1R expression in breast cancer and its relationship with tamoxifen resistance based on public databases

作　　者：童璐 欧阳慧婷 邹联洪[1] 易嘉宁 曾杰[1] 范培芝[1] Lu Tong;Huiting Ou-yang;Lianhong Zou;Jianing Yi;Jie Zeng;Peizhi Fan(The First Affiliated Hospital of Hunan Normal University/Hunan Provincial People's Hospital,Changsha 410005,China)

机构地区：[1]湖南师范大学附属第一医院/湖南省人民医院,长沙410005

出　　处：《湖南师范大学学报（医学版）》2022年第5期32-38,共7页Journal of Hunan Normal University(Medical Sciences)

基　　金：湖南省卫健委科研项目资助(202204012854)。

摘　　要：目的 :研究NPY1R在乳腺癌他莫昔芬耐药中的作用,为预测和逆转乳腺癌内分泌耐药提供新的分子标志物。方法 :从GEO数据库中获取乳腺癌他莫昔芬耐药前后基因表达数据集,并通过GEO2R筛选出NPY1R为乳腺癌他莫昔芬耐药前后差异表达基因,利用TCGA数据库和CPTAC数据库分析NPY1R在乳腺癌组织中的mRNA和蛋白表达水平,收集我院临床组织样本并通过免疫组化验证NPY1R在他莫昔芬耐药前后的配对组织中的差异,通过STRING数据库构建NPY1R编码蛋白互作网络并进行GO/KEGG分析以及利用starBase数据库预测靶向作用于NPY1R的miRNAs;最后使用Kaplan-Meier Plotter数据库分析NPY1R在乳腺癌患者中的生存及预后。结果 :与正常组织比较,NPY1R在乳腺癌中mRNA表达下调且其编码蛋白表达水平也同样降低;免疫组化结果显示NPY1R在乳腺癌他莫昔芬耐药后复发组织中表达下降;临床相关性分析发现NPY1R的表达与乳腺癌中ER、PR、Her2状态显著相关;GO/KEGG分析显示NPY1R及其相关蛋白主要作用于G蛋白偶联受体等信号通路,star Base预测mi RNA-224-5p和miRNA-212-3p可能靶向作用于NPY1R;通过生存分析发现低表达NPY1R基因的乳腺癌患者伴随着较差的预后。结论 :NPY1R为他莫昔芬耐药的相关基因,其表达下调可能与乳腺癌细胞产生他莫昔芬药物抵抗相关,有效发掘这些内分泌治疗耐药相关差异表达基因中的数据信息,为乳腺癌内分泌抵抗提供新的治疗方向。Objective To explore the role of NPY1R in tamoxifen resistance and provide a new molecular marker for predicting and reversing endocrine resistance in breast cancer. Methods The gene expression data set of breast cancer before and after tamoxifen resistance was obtained from GEO database, and NPY1R was selected as the differential expression gene of breast cancer before and after tamoxifen resistance by GEO2R. The mRNA and protein expression level of NPY1R in breast cancer was analyzed by TCGA database and CPTAC database, and the clinical tissue samples of our hospital were collected and the expression difference of NPY1R in matched tissues before and after tamoxifen resistance was verified by immunohistochemistry. The NPY1R-encoded protein interaction network was constructed through the STRING database and further analyzed by GO/KEGG, and then, using starBase to predict the miRNAs. Finally, the Kaplan-Meier Plotter database was used to analyze the survival and prognosis of NPY1R in breast cancer patients. Results Compared with normal breast tissues, the mRNA expression of NPY1R in breast cancer tissues was down-regulated and the expression level of its encoded protein was also inhibited. Immunohistochemical results showed that the expression of NPY1R decreased in breast cancer recurrence tissues after tamoxifen resistance, and clinical correlation analysis stated that the expression of NPY1R was significantly correlated with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer. GO/KEGG analysis proved that NPY1R and its related proteins mainly act on G protein-coupled receptors signaling pathway and miRNA-224-5p and miRNA-212-3p may target NPY1R. Survival analysis illustrated that breast cancer patients with low expression of NPY1R gene had poor prognosis. Conclusion NPY1R is a gene related to tamoxifen resistance, and its down-regulation may be related to tamoxifen resistance in breast cancer. It can effectively explore the data information in these differential

关 键 词：乳腺癌 内分泌耐药 NPY1R 他莫昔芬 生物信息分析 

分 类 号：R737.9[医药卫生—肿瘤]