RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
E2F2 作为浆液性卵巢癌潜在预后生物标志物的整合分析及实验验证及其致癌作用
英文原题：Integrated analysis and experimental validation of E2F2 as a potential prognostic biomarker and its oncogenic roles in serous ovarian cancer.
查看英文原题
Integrated analysis and experimental validation of E2F2 as a potential prognostic biomarker and its oncogenic roles in serous ovarian cancer.
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研究概要
E2F2 高表达标志着 SOC 患者预后不良和免疫细胞浸润，因此可作为独立危险因素。它可能作为诊断、患者分层和指导个性化治疗的潜在生物标志物。进一步研究可改善 SOC 管理。
研究思路结论见上方概要
背景
本研究评估了E2F转录因子2（E2F2）在浆液性卵巢癌（SOCs）中的预后作用，并探讨了其生物学功能、免疫细胞浸润联系及治疗意义。
方法
整合TCGA/Genotype-Tissue Expression (GTEx)数据，我们使用生物信息学工具（ssGSEA、Immunophenoscore和oncoPredict）分析通路和治疗反应。验证涉及RT-qPCR、Western blot分析、细胞毒性及transwell实验。
结果
E2F2在SOC肿瘤中表达上调，与较差的总生存期/无病生存期及更高的肿瘤分级相关。五个细胞周期相关基因（ORC1、RAD54L、CCNF、NCAPH和HASPIN）表现出强共表达。对808个差异表达基因的通路分析将E2F2与免疫细胞募集联系起来，包括CD4+ T细胞、NK细胞和Tregs；低E2F2水平与更高的免疫评分相关。高E2F2预测对化疗/靶向治疗的敏感性，而低E2F2与抗CTLA4反应性相关。在体外，E2F2促进转移。
展开英文摘要原文
BACKGROUND
This study evaluated the prognostic role of E2F transcription factor 2 (E2F2) in serous ovarian cancers (SOCs) and explored its biological functions, immune cell infiltration links, and therapeutic implications.
METHODS
Integrating TCGA/Genotype-Tissue Expression (GTEx) data, we used bioinformatics tools (ssGSEA, Immunophenoscore, and oncoPredict) to analyze pathways and treatment responses. Validation involved RT-qPCR, Western blot analysis, cytotoxicity, and transwell assays.
RESULTS
E2F2 was upregulated in SOC tumors, correlating with poorer overall/disease-free survival and higher tumor grade. Five cell-cycle-related genes ( ORC1 , RAD54L , CCNF , NCAPH , and HASPIN ) showed strong co-expression. A pathway analysis of 808 differentially expressed genes linked E2F2 to immune cell recruitment, including CD4 + T cells, NK cells, and Tregs; low E2F2 levels were associated with higher immune scores. High E2F2 predicted sensitivity to chemotherapy/targeted therapy, while low E2F2 correlated with anti-CTLA4 responsiveness. In vitro , E2F2 promoted metastasis.
CONCLUSION
High E2F2 expression marks poor prognosis and immune cell infiltration in SOCs and thus acts as an independent risk factor. It may serve as a potential biomarker for diagnosis, patient stratification, and guiding personalized therapy. Further research could enhance SOC management.
论文信息
- 作者
- Jiang F、Fei H、Yang L、Chen R、Zhang L
- 单位
- Department of Gynecology & Obstetrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.China
- 期刊
- Frontiers in molecular biosciences2025
- 原文标识
- PubMed 41064634 · DOI 10.3389/fmolb.2025.1661558
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