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作 者:吴紫云 汪嵘嵘 俞快 谢玉芬 吴佳慧 刘晓萍 周伯宣 熊海蔚[1] WU Zi-yun;WANG Rong-rong;YU Kuai;XIE Yu-fen;WU Jia-hui;LIU Xiao-ping;ZHOU Bo-xuan;XIONG Hai-wei(Specialist Breast Center,the First Affiliated Hospital,the First Affiliated Hospital,Nanchang University,Nanchang 330006,China;Class of 2021,the First Clinical Medical College,the First Affiliated Hospital,Nanchang University,Nanchang 330006,China;Department of Blood Transfusion,the First Affiliated Hospital,Nanchang University,Nanchang 330006,China;Jiangxi Provincial Key Laboratory of Blood Transfusion Medicine,Nanchang 330006,China)
机构地区:[1]南昌大学第一附属医院乳腺专病中心,南昌330006 [2]南昌大学第一临床医学院,南昌330006 [3]南昌大学第一附属医院输血医学科,南昌330006 [4]输血医学江西省重点实验室,南昌330006
出 处:《南昌大学学报(医学版)》2024年第5期1-9,共9页Journal of Nanchang University:Medical Sciences
基 金:国家自然科学基金资助项目(32100729);江西省科技厅重大科技研发专项“揭榜挂帅”制项目(20213AAG01013);江西省主要学科学术和技术带头人培养计划-领军人才项目(20213BCJ22015);江西省科技创新基地计划(20212BCD42006);江西省教育厅重点项目(GJJ200131)。
摘 要:目的探讨聚蛋白聚糖(aggrecan,ACAN)在泛癌中的表达,并聚焦乳腺癌分析其临床预后意义、免疫细胞浸润及功能富集分析。方法采用生物信息学分析ACAN在多种肿瘤组织及正常组织中的表达、临床预后;运用GEPIA 2、UALCAN、The Human Protein Altas多组学数据库分析ACAN在乳腺癌和正常乳腺组织中的表达;采用TCGA数据库分析ACAN在乳腺癌中的表达水平与临床病理参数及预后的关系;利用TIMER2.0数据库分析ACAN在乳腺癌中的表达水平与免疫细胞浸润的关系,并进一步了解ACAN与免疫检查点的关系;利用GeneMANIA和STRING数据库构建ACAN基因与蛋白质互作网络;运用Metascape数据库对ACAN相关基因进行功能富集分析。结果ACAN在多种肿瘤组织中差异表达,在乳腺癌组织中呈现高表达且为预后不良因素(P<0.05);ACAN高表达与T、B淋巴细胞低浸润、巨噬细胞和中性粒细胞高浸润相关(P<0.05);ACAN与ADAMTS4、ADAMTS5、HAPLN1及COMP相互作用并参与人体多种生物学过程。结论ACAN在乳腺癌中表达水平增高,且ACAN高表达的乳腺癌患者预后较差,其机制可能与抑制T、B淋巴细胞浸润,促进巨噬细胞、中性粒细胞浸润有关。Objective To explore the expression of aggrecan(ACAN)in pan-cancers,and focus on breast cancer to analyze its clinical prognostic significance,immune cell infiltration and functional enrichment analysis.Methods Bioinformatics was used to analyze the expression and clinical prognosis of ACAN in a variety of tumor tissues and normal tissues;the multi-omics databases of GEPIA 2,UALCAN,and The Human Protein Altas were used to analyze the expression of ACAN in breast cancer and normal breast tissues;the TCGA database was used to analyze the relationship between the expression level of ACAN in breast cancer and the clinicopathologic parameters and prognosis;TIMER2.0 database was used to analyze the relationship between ACAN expression level and immune cell infiltration in breast cancer,and to further understand the relationship between ACAN and immune checkpoints;GeneMANIA and STRING database were used to construct the ACAN gene-protein interaction network;functional enrichment analysis of ACAN-related genes was carried out using the Metascape database.Results ACAN showed varied expressions in multiple tumor types,with notably high levels in breast cancer tissues,indicating as a poor prognosis factor;high expression of ACAN was correlated with low infiltration of T and B lymphocytes,and high infiltration of macrophages and neutrophils(P<0.05);ACAN interacted with ADAMTS4,ADAMTS5,HAPLN1,and COMP and was involved in multiple biological processes in the human body.Conclusion ACAN expression level is elevated in breast cancer,and breast cancer patients with high ACAN expression have a poor prognosis.The mechanism may be related to the inhibition of T and B lymphocyte infiltration and the promotion of macrophage and neutrophil infiltration.
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