胃癌是全球高发的消化系统恶性肿瘤,其复发率高且预后不良,亟需寻找新的分子靶点以提高诊治效果。E2F转录因子1(E2F transcription factor 1, E2F1)是细胞周期调控的核心转录因子,近年来其在胃癌中的异常表达及生物学作用逐渐显现重要临床意义。多项组织芯片与数据库研究表明,E2F1在胃癌组织中普遍高表达,并在不同分期和病理类型中呈异质性分布,其水平与分化程度、浸润深度及生存结局密切相关。E2F1不仅通过调控 DNA 拓扑异构酶Ⅱα、细胞周期依赖性激酶6和细胞分裂周期蛋白25B等下游靶点推动细胞周期进程,还参与凋亡调节、上皮-间质转化、肿瘤干性维持以及免疫抑制性微环境的构建。特别是在干性维持和化疗耐药中,E2F1与多种非编码RNA 形成复杂互作网络,进而增强胃癌细胞的侵袭性。此外,研究发现E2F1与调节性T细胞、M2型肿瘤相关巨噬细胞以及耗竭性CD8阳性T 细胞等免疫抑制性细胞的富集密切相关, 提示其在免疫逃逸中发挥关键作用。综上,E2F1在胃癌发生发展中展现出多维度的调控功能, 具有潜在的诊断、预后及治疗价值,为后续靶向干预及联合免疫治疗提供了理论依据。

Gastric cancer, as a highly prevalent malignant tumor of the digestive system worldwide, demands the identification of new molecular targets given its high recurrence rate and poor prognosis.E2F Transcription Factor 1(E2F1), a core transcription factor of cell cycle regulation, has been shown to exert important roles in gastric cancer via its aberrant expression and functional alterations. Several tissue microarray and database studies have shown that E2F1 is highly expressed in gastric cancer tissues, with its expression level varying across different stages and pathological subtypes. Moreover, its expression significantly correlates with the degree of tumor differentiation, depth of invasion, and patient survival outcomes. Mechanistically, E2F1 not only promotes cell cycle progression by regulating downstream targets such as DNA topoisomerase II alpha, cyclin-dependent kinase 6 and cell division cycle 25B, but also participates in apoptosis regulation, epithelial-mesenchymal transition, stemness maintenance, and immunosuppressive microenvironment construction. Especially in maintaining tumor stemness and driving chemoresistance, E2F1 interacts with various non-coding RNAs to enhance the invasiveness of gastric cancer cells. Further studies have revealed that high E2F1 expression is associated with increased infiltration of immunosuppressive cells, including regulatory T cells, M2-polarized tumor-associated macrophages, and exhausted CD8+ T cells, highlighting its pivotal role in facilitating immune evasion. In conclusion, E2F1 plays a multidimensional regulatory role in the development of gastric cancer, endowing it with potential diagnostic, prognostic and therapeutic intervention value, and provides a theoretical basis for the subsequent targeted therapy and combined immunotherapy.