陈昕 1何蓥飞 2尹志东 2徐熙 2孔艳茹 1陈峥妍 3张静 2孙博浩2
作者信息
- 1. 浙江大学医学院附属第一医院病理科,浙江 杭州 310006
- 2. 浙江大学医学院附属第二医院病理科,浙江 杭州 310009
- 3. 宁波大学附属第一医院病案室,浙江 宁波 315000
- 折叠
摘要
Abstract
Objective To elucidate the expression profile of mucin 1(MUC1)in gliomas,assess its impact on the prognosis of glioma patients,define the pathways through which MUC1 contributes to glioma pathogenesis,and evaluate its potential as a novel therapeutic target.Methods An integrated analysis was conducted utilizing glioma data sets from The Cancer Genome Atlas(TCGA)database and the data of normal brain tissues from the Genotype-Tissue Expression(GTEx)database.The functional impact of the MUC1 gene was evaluated through Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA).Single-sample GSEA(ssGSEA)was employed to assess the correlation between MUC1 expression and immune cell infiltration.Addition-ally,the relationship between MUC1 expression and clinical parameters was examined.From February 12th,2023,to March 7th,2024,tissue samples from 30 glioma patients were collected at the Second Affiliated Hospital of Zhejiang University School of Medicine.Immunohisto-chemistry was used to evaluate MUC1 expression in these samples.Results In the TCGA and GTEx databases,MUC1 was overexpressed in glioma tissues,compared to normal brain tissues,and its expression was significantly correlated with worse prognosis of the patients(P<0.01).High MUC1 expression in glioma was correlated with increased infiltration of immune cells,including macrophages(r=0.575,P<0.01),neutrophils(r=0.471,P<0.01),and dendritic cells(r=0.446,P<0.01),while showing a negative correlation with regulatory T cells(r=-0.137,P<0.01)and plasmacytoid dendritic cells(r=-0.119,P<0.01).An analysis of differentially expressed genes from glioma samples within the TCGA database identified serum amyloid A1(SAA1),peptidase inhibitor 3(PI3),SAA2,and phospholipase A2 group ⅡA(PLA-2G2A)as genes co-expressed with MUC1,with lower expression levels of these genes being linked to improved survival outcomes.GO and KEGG pathway analyses emphasized MUC1's involvement in critical pathways in glioma,including the interleukin 17(IL-17)signaling pathway and cytokine-cytokine receptor interactions.High MUC1 expression was associated with high World Health Organization(WHO)grades,isocitrate dehydrogenase(IDH)wild-type status,1p/19q non-codel status,and poor survival prognosis(all P<0.01).Immunohisto-chemistry analysis revealed that MUC1 expression was significantly higher in glioma tissues than in adjacent normal tissues in the 30 glio-ma cases.Conclusions MUC1 plays a significant role in glioma biology and is a potential independent prognostic marker.MUC1 possibly plays a crucial role in mediating immune infiltration in glioma.关键词
胶质瘤/黏蛋白1/免疫浸润/预后Key words
glioma/mucin 1/immune infiltration/prognosis