南方医科大学学报2025，Vol.45Issue(5)：1063-1073,11.DOI:10.12122/j.issn.1673-4254.2025.05.20
WW结构域E3泛素连接酶1调控卵巢癌肿瘤微环境中的免疫浸润
WW domain-containing ubiquitin E3 ligase 1 regulates immune infiltration in tumor microenvironment of ovarian cancer
摘要
Abstract
Objective To explore the association of the expression of WW domain-containing ubiquitin E3 ligase 1(WWP1)with immune infiltration in tumor microenvironment(TME)of ovarian cancer.Methods Ovarian cancer patient data from The Cancer Genome Atlas(TCGA)were used to analyze the association of WWP1 expression with patient prognosis.TISCH2 was utilized to analyze the changes in immune cell subtypes in TME of metastatic tumor and after chemotherapy.The impact of WWP1 on immune cell infiltration,somatic copy number alterations of WWP1 and evolution of immune cell subtypes was evaluated using TIMER and TIGER pseudo-time analysis.A deep learning model was used to analyze TCGA pathological images to investigate the effect of WWP1 on TME of ovarian cancer.RNA-seq analysis was conducted to identify the differentially expressed genes in WWP1-overexpressing SKOV3 cells and validate immune infiltration.Multicolor immunofluorescence assay was used to analyze the immune markers in SKOV3 and SKOV3/DDP cell xenografts in nude mice.Results The patients with high WWP1 expression levels had significantly lower overall survival rate(P=0.0012).High WWP1 expression levels and Stage IV disease were both associated with a poor prognosis(P<0.05).In metastatic ovarian cancer or after chemotherapy,the percentages of malignant tumor cells and tumor-associated fibroblasts increased in the TME,accompanied by elevated WWP1 levels.WWP1 expression level was positively correlated with pro-tumorigenic immunosuppressive cells(r=0.1323-0.3955,P<0.05)and negatively with tumor-inhibiting immune cells(r=-0.1949--0.1333,P<0.05).Specific copy number alterations of WWP1 also influenced CD8+T cell percentage and neutrophil infiltration levels in the TME.RNA-seq analysis of WWP1-overexpressing SKOV3 cells and immunofluorescence assay of the tumor-bearing mice yielded findings consistent with those of bioinformatics analysis.Conclusion WWP1 may serve as a prognostic biomarker and a potential target for immune regulation in the TME of ovarian cancer.关键词
卵巢癌/WW结构域E3泛素连接酶1/免疫浸润/肿瘤微环境Key words
ovarian cancer/WW domain-containing ubiquitin E3 ligase 1/immune infiltration/tumor microenvironment引用本文复制引用
郭晓娟,杜瑞娟,陈丽平,郭克磊,周彪,卞华,韩立..WW结构域E3泛素连接酶1调控卵巢癌肿瘤微环境中的免疫浸润[J].南方医科大学学报,2025,45(5):1063-1073,11.基金项目
国家自然科学基金(82074076) （82074076）
河南省科技攻关项目(242102311268)Supported by National Natural Science Foundation of China(82074076). （242102311268）
