{"id":398,"title":"The Characteristics of Tumor Microenvironment by the Single Cell Profile in Endometrial Cancer of no Specific Molecular Profile (NSMP) Subtype","title_zh":"无特定分子分型子宫内膜癌的单细胞图谱揭示肿瘤微环境特征与复发相关机制","url":"https://pubmed.ncbi.nlm.nih.gov/42902496","doi":"10.1002/advs.78332","pmid":"42902496","journal":"Adv Sci (Weinh)","kind":"paper","lang":"en","published_at":"2026-10-20T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Yuan X","Zhai Z","Jing C","Zhang W","Tian W","Ren Y"],"primary_topic":"endometrium","topics":[{"slug":"omics-methods","score":5.0,"hits":["rna sequencing","single cell","spatial transcriptomics"]},{"slug":"endometrium","score":4.0,"hits":["endometrial"]},{"slug":"ethics-policy","score":1.0,"hits":["regulatory"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":67.0,"final_score":73.0,"score_dims":{"novelty":75,"rigor":78,"impact":60,"relevance":45,"translation":50},"recommend_reason":"多组学整合较扎实，提出SPP1+巨噬细胞重塑NSMP子宫内膜癌免疫微环境并关联复发的新机制；但主题偏肿瘤微环境与肿瘤复发，与辅助生殖核心临床距离较远，适合关注子宫内膜病理/免疫微环境者浏览。","keywords":["子宫内膜癌","无特定分子分型","肿瘤微环境","单核RNA测序","空间转录组","SPP1+巨噬细胞"],"selected":1,"story_id":358,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"adv-sci","journal_tier":"general-top","journal_if":14.3,"is_mock":false,"summary_zh":"该研究整合单核RNA测序、空间转录组与多重免疫组化，解析无特定分子分型（NSMP）子宫内膜癌的肿瘤微环境及复发机制。发现免疫浸润减少、免疫抑制细胞（SPP1+巨噬细胞、Treg）增多；复发前原发瘤中高干性上皮细胞簇增多；tip内皮细胞及MMP11+LEF1+ CAF与血管生成和上皮-间质转化相关，CD4+ T细胞处于应激状态且功能受损。SPP1+ TAM可能经SPP1-CD44促进CD4+ T细胞应激并维持上皮干性，体外实验验证。","summary":"Endometrial cancer (EC) of no specific molecular profile (NSMP) subtype lacks specific molecular features, and the relationship of tumor microenvironment (TME) and relapse in NSMP EC remains incompletely understood. This study integrates single-nucleus RNA sequencing, spatial transcriptomics, and multiplex immunohistochemistry to elucidate the TME and mechanisms of relapse in NSMP EC. The results showed reduced immune infiltration and increased immune-suppressive cells, including SPP1+ macrophages and regulatory T cells (Tregs) in NSMP EC. More epithelial cell clusters with high stemness scores are observed in primary NSMP EC tumors collected before recurrence. In NSMP EC, tip endothelial cells and MMP11+ LEF1+ cancer-associated fibroblasts (CAFs) are linked with angiogenesis and epithelial-mesenchymal transition, and CD4+ T cells remain in a stress-response state and are functionally impaired. Interestingly, a subset of tumor-associated macrophages (TAMs) characterized by SPP1 expression is discovered, which may remodel the tumor microenvironment by potentially promoting CD4+ T cells stress and maintaining epithelial cells stemness through SPP1-CD44, thereby potentially contributing to the proliferation and migration of tumor cells, which has verified by in vitro experiments. This study advances the mechanistic understanding of recurrence-related TME and provides a foundation for the development of personalized treatments for NSMP EC patients.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}