增强子RNA A2MP1在肺腺癌中的临床意义与分子机制  

Clinical significance and molecular mechanism of enhancer RNA A2MP1 in lung adenocarcinoma

作　　者：马甜甜 朱翠雯 段怡平 陈梁玥 李东旭 张晓洋 喻明霞[1] 杨桂[1] MA Tiantian;ZHU Cuiwen;DUAN Yiping;CHEN Liangyue;LI Dongxu;ZHANG Xiaoyang;YU Mingxia;YANG Gui(Department of Laboratory Medicine,Zhongnan Hospital of Wuhan University,Wuhan,Hubei,China,430071)

机构地区：[1]武汉大学中南医院检验科,湖北武汉430071

出　　处：《分子诊断与治疗杂志》2025年第3期395-399,共5页Journal of Molecular Diagnostics and Therapy

基　　金：国家自然科学基金(81472033、30901308);湖北省卫生健康科研基金资助(WJ2019M203);湖北省卫生和计划生育委员会联合基金项目(WJ2018H0028);湖北省卫生和计划生育委员会青年人才项目(WJ2015Q021);武汉市应用基础研究(2017060201010171);武汉大学中南医院科技创新培育基金(cxpy2018031、cxpy20160054);武汉大学大学生创新项目(MS2017045、S2018301747)。

摘　　要：目的研究增强子RNA(eRNA)A2MP1在肺腺癌(LUAD)中的表达和关键靶基因预测,分析A2MP1在LUAD恶性进展中的分子机制及其与靶基因相关性,探讨A2MP1在LUAD患者中的预后作用。方法在UCSC Xena数据库中下载33类肿瘤的表达数据、生存数据和临床数据。已报道的eRNA及其调控的基因被选择为假定的eRNA-靶基因对。采用Kaplan-Meier生存分析和相关性分析确定关键的eRNA。A2MP1以PZP为靶点,被鉴定为与LUAD相关的eRNA。使用χ^(2)检验分析A2MP1表达与患者临床病理的相关性;通过泛癌数据对结果进行验证;利用GO和KEGG富集分析探索A2MP1在LUAD中参与的信号途径。结果利用PreSTIGE算法与Kaplan-Meier生存分析和相关性分析,筛选出A2MP1作为目的基因,并选定PZP作为靶基因。A2MP1的表达水平与患者的临床分期(P<0.05)、肿瘤大小(P<0.05)、淋巴结转移(P<0.05)显著相关。A2MP1低表达组患者的总体生存率显著低于高表达组患者,差异有统计学意义(P<0.05)。GO结果表明,A2MP1与T细胞的活化、淋巴细胞和单个核细胞分化、抗原受体介导的信号通路、免疫反应-激活细胞表面受体信号通路等多种免疫途径密切相关。在KEGG通路分析中,PI3K/AKT和JAK-STAT信号途径被富集。泛癌验证表明头颈鳞状细胞癌、胸腺癌、肾透明细胞癌、急性髓细胞样白血病、脑低级别胶质瘤、皮肤黑色素瘤等癌症中高表达A2MP1组中患者的总体生存率高于低表达组,差异有统计学意义(P<0.05),且A2MP1和PZP在这些癌症中均显示出显著的相关性(P<0.05)。结论A2MP1是肺腺癌中与生存相关的关键eRNA,由于A2MP1在免疫微环境和PI3K/AKT、JAK-STAT信号通路方面的潜在作用,可能成为肺腺癌患者新的免疫治疗靶点。Objective To study the expression and key target gene prediction of eRNA A2MP1 in lung adenocarcinoma(LUAD),analyze the molecular mechanism of A2MP1 in the malignant progression of LUAD and its correlation with target genes,and explore the prognostic role of A2MP1 in LUAD patients.Methods Expression data,survival data and clinical data of 33 tumors were downloaded from the UCSC Xena database.The reported enhancer RNA(eRNA)and the genes it regulates were selected as putative eRNAtarget gene pairs.Kaplan-Meier survival analysis and correlation analysis were used to identify key eRNA.A2MP1 targets PZP and has been identified as a LUAD-related eRNA.The χ^(2) test was used to analyze the association between A2MP1 expression and clinicopathology.The results were validated with pan-cancer data.GO and KEGG enrichment analysis were used to explore the signaling pathways involved in A2MP1 in LUAD.Results The target gene A2MP1 and PZP were selected using the PreSTIGE algorithm,Kaplan-Meier survival analysis,and correlation analysis.A2MP1 expression was significantly correlated with clinical stage(P<0.05),tumor size(P<0.05),and lymph node metastasis(P<0.05).Patients with low A2MP1 expressions had a significantly lower overall survival rate compared to those with high A2MP1 expressions,with a statistically significant(P<0.05).GO analysis revealed that A2MP1 is closely associated with various immune pathways,including T cell activation,lymphocyte and mononuclear cell differentiation,antigen receptor-mediated signaling pathways showed enrichment of the PI3K/AKT and JAK-STAT signal pathways.Pan-cancer validation demonstrated that patients in the high-expression A2MP1 group had a higher overall survival rate in cancers such as head and neck squamous cell carcinoma,thymic carcinoma,clear cell renal carcinoma,acute myeloid leukemia,low-grade glioma of the brain,and cutaneous melanoma compared to the low-expression group,with a statistically significant difference(P<0.05).A significant correlation between A2MP1 and PZP was observed

关 键 词：肺腺癌 A2MP1 eRNA 预后 

分 类 号：R73[医药卫生—肿瘤]