新医学2025，Vol.56Issue(4)：361-371,11.DOI:10.12464/j.issn.0253-9802.2025-0056
CLEC7A调节PD-L1促进卵巢癌生长的作用及机制研究
The role and mechanism of CLEC7A in regulating PD-L1 to promote ovarian cancer growth
摘要
Abstract
Objective To elucidate the role of C-type lectin domain family 7 member A(CLEC7A)in high-grade serous ovarian carcinoma(HGSOC)and its underlying mechanisms.Methods Using the Cancer Genome Atlas-Ovarian Cancer(CGA-OV)dataset,combined with transcriptional regulatory network analysis and master regulator analysis(MRA),the impact of CLEC7A on immune-related genes in HGSOC was determined.Pathway enrichment analysis and validation identified the regulatory mechanism of CLEC7A on the Janus Kinase(JAK)/signal transducer and activator of transcription 3(STAT3)pathway.The GSE184880 single-cell sequencing dataset was analyzed to reveal differences in immune cell proportions and cellular communication between CLEC7A low-expression and high-expression HGSOC tumors.Paraffin-embedded tumor tissues and corresponding adjacent tissues,along with clinicopathological data,were collected from 70 HGSOC and 70 ovarian clear cell carcinoma(OCCC)patients diagnosed and surgically treated at the First Affiliated Hospital of the University of Science and Technology of China/Anhui Provincial Hospital between January 2017 and December 2022.Differences in prognostic factors between HGSOC and OCCC were compared.Immunohistochemical staining was used to detect the expression levels of CLEC7A and PD-L1 in HGSOC,OCCC,and corresponding adjacent tissues.A short hairpin RNA(shRNA)vector targeting CLEC7A was constructed to assess changes in the proliferation and apoptosis of HGSOC cells both after CLEC7A inhibition.In a mouse tumor model with high CLEC7A expression,the proportion of myeloid-derived suppressor cells(MDSCs)and CD8+T cells,as well as the functional changes of MDSCs,were observed.Results Transcriptional regulatory network analysis revealed that forkhead box protein P3(FOXP3)and CLEC7A both regulate immune-related genes.CLEC7A was not only correlated with overall patient survival but also highly expressed in HGSOC tumor tissues(all P<0.05).Knockdown of CLEC7A promoted apoptosis and inhibited the proliferation of HGSOC cell lines both in vitro and in vivo(all P<0.05).CLEC7A regulated the expression of programmed death ligand-1(PD-L1)through the JAK/STAT3 signaling pathway.In CLEC7A high-expressing tumor tissues,the proportion of CD8+T cells decreased,while the proportion of MDSCs increased,and the functionality of MDSCs was enhanced(all P<0.05).Conclusion CLEC7A induces PD-L1 expression in HGSOC,promotes HGSOC proliferation,and activates immunosuppressive signaling pathways,potentially leading to the malignant growth of HGSOC.关键词
C型凝集素结构域家族 7 成员/高级别浆液性卵巢癌/程序性死亡配体-1/JAK/STAT3 通路/肿瘤免疫Key words
CLEC7A/High-grade serous ovarian carcinoma/PD-L1/JAK/STAT3 pathway/Tumor immunity引用本文复制引用
陈瑶,孙思柏,许俊,何杰..CLEC7A调节PD-L1促进卵巢癌生长的作用及机制研究[J].新医学,2025,56(4):361-371,11.基金项目
国家自然科学基金(81872055) （81872055）
