基于生物信息学分析PITX1在乳腺癌中的表达及预后意义  

Bioinformatics analysis of the expression and prognostic significance of PITX1 in breast cancer

作　　者：葛新[1] 王文东 GE Xin;WANG Wen-dong(Department of Breast Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院乳腺外科,郑州450052

出　　处：《医药论坛杂志》2024年第18期1905-1910,1916,共7页Journal of Medical Forum

基　　金：河南省自然科学基金项目(202300410395);河南省医学科技攻关计划联合共建项目(LHGJ20230188)。

摘　　要：目的研究垂体同源框配对同源域转录因子1(paired-like homolog 1,PITX1)基因在乳腺癌中表达及其与患者预后关系。方法通过癌症基因组图谱(the cancer genome atlas,TCGA)数据库分析PITX1的mRNA在正常组织及乳腺癌组织中的表达差异。受试者工作特征(receiver operating characteristic,ROC)曲线获得区分乳腺癌与正常乳腺组织的PITX1最佳截断值。获取人类蛋白组图谱(the human protein atlas,THPA)数据库PITX1蛋白表达情况,通过Kaplan-Meier Plotter数据库检索PITX1与乳腺癌预后的相关性。利用STRING数据库构建蛋白质相互作用(protein-protein interaction,PPI)网络,利用肿瘤免疫浸润TIMER数据库评估肿瘤免疫浸润细胞与PITX1之间的关系。结果乳腺癌组织中PITX1的mRNA和蛋白表达水平高于正常组织,癌组织中PITX1启动子甲基化水平显著低于正常乳腺组织。PITX1高表达的乳腺癌患者总生存期及无复发生存期更短,差异具有统计学意义(P<0.05)。ROC曲线表明,PITX1区分乳腺癌与正常组织的AUC值为0.918(95%CI:0.899~0.936)。PITX1结合10种蛋白,功能富集分析其在基因转录调控中起到多种作用。PITX1表达与T细胞(r=0.084,P<0.01)、B细胞(r=0.080,P<0.01)及巨噬细胞(r=0.083,P<0.01)的浸润丰度具有正相关性,与T辅助细胞(r=-0.111,P<0.001)浸润丰度具有负相关性。结论PITX1与乳腺癌预后及免疫浸润关系密切,可成为乳腺癌预后生物标志物及免疫治疗的新靶点。Objective To investigate the expression of the pituitary homeobox gene paired-like homolog 1(PITX1)in breast cancer and its prognostic relevance for patients.Methods The expression difference of PITX1 mRNA in normal tissues and breast cancer was investigated through analysis of the cancer genome atlas(TCGA)database.Receiver operating characteristic(ROC)curve was utilized to determine the optimal cutoff value of PITX1 for discriminating breast cancer from normal breast tissue.Protein expression data for PITX1 was obtained from the human protein atlas(THPA)database,and its association with breast cancer prognosis was assessed using the Kaplan-Meier Plotter database.Furthermore,a protein-protein interaction(PPI)network was established with the STRING database,and the correlation between PITX1 and tumor immune infiltrating cells was evaluated through the tumor immune estimation resourse(TIMER)database.Results In breast cancer,the mRNA and protein levels of PITX1 were elevated compared to those in normal tissues,while the methylation level of the PITX1 promoter in cancer tissues was markedly lower than in normal breast tissues.Breast cancer patients exhibiting high PITX1 expression experienced reduced overall survival and recurrence-free survival rates,and the difference was statistically significant(P<0.05).Analysis using the ROC curve reveals an AUC value of 0.918(95%CI:0.899~0.936)for the differentiation of breast cancer from normal tissues based on PITX1 expression.PITX1 bound to 10 proteins and played a variety of roles in gene transcriptional regulation.Additionally,the expression of PITX1 demonstrated a positive correlation with the infiltration levels of T cells(r=0.084,P<0.01),B cells(r=0.080,P<0.01),and macrophages(r=0.083,P<0.01),while showing a negative correlation with the infiltration levels of T helper cells(r=-0.111,P<0.001).Conclusion PITX1 is significantly associated with both the prognosis and immune infiltration in breast cancer.It can be utilized as a novel biomarker for predicting prognosis in br

关 键 词：垂体同源框配对同源域转录因子1 生物标志物 乳腺癌 免疫浸润细胞 

分 类 号：R737.9[医药卫生—肿瘤]