Integrated analysis and experimental validation of E2F2 as a potential prognostic biomarker and its oncogenic roles in serous ovarian cancer.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-09-23 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1661558

Fengyin Jiang, He Fei, Lina Yang, Rujun Chen, Liwen Zhang

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引用次数: 0

Abstract

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.

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E2F2作为潜在的预后生物标志物及其在浆液性卵巢癌中的致癌作用的综合分析和实验验证。

背景：本研究评估了E2F转录因子2 （E2F2）在浆液性卵巢癌（soc）中的预后作用，并探讨了其生物学功能、免疫细胞浸润联系和治疗意义。方法：整合TCGA/基因型组织表达（GTEx）数据，使用生物信息学工具（ssGSEA、Immunophenoscore和oncopdict）分析通路和治疗反应。验证包括RT-qPCR、Western blot分析、细胞毒性和transwell分析。结果：E2F2在SOC肿瘤中表达上调，与较差的总生存/无病生存和较高的肿瘤分级相关。5个细胞周期相关基因（ORC1、RAD54L、CCNF、NCAPH、HASPIN）表现出强共表达。808个E2F2与免疫细胞募集相关的差异表达基因的通路分析，包括CD4+ T细胞、NK细胞和Tregs；低E2F2水平与较高的免疫评分相关。高E2F2预测化疗/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。结论：E2F2高表达标志着SOCs预后不良和免疫细胞浸润，是独立的危险因素。它可以作为诊断、患者分层和指导个性化治疗的潜在生物标志物。进一步的研究可以加强SOC的管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.