文章：

IL4I1作为P53突变型子宫内膜癌治疗靶点的蛋白质组学鉴定

Proteomic Identification of IL4I1 as a Therapeutic Target in P53-Mutant Endometrial Cancer

原文发布日期：12 September 2025

DOI: 10.3390/cancers17182986

类型: Article

开放获取: 是

英文摘要：

Background: Endometrial cancer (EC) is one of the most common gynecologic malignancies, with a rising incidence worldwide. The Cancer Genome Atlas (TCGA) classifies EC into four molecular subtypes, among which the high-copy number subtype is characterized by TP53 mutations and associated with poor prognosis. However, this subtype remains understudied. IL4I1, an immunoregulatory enzyme implicated in various cancers, has emerged as a potential biomarker for tumor progression. This study aimed to explore IL4I1 as a prognostic marker in P53-mutant EC and to identify its potential as a therapeutic target.Methods: We retrospectively analyzed clinical data from 495 EC patients and selected 33 P53-mutant cases using Sanger sequencing and immunohistochemistry. Tumor tissues were collected via laser capture microdissection, stratified by five-year survival outcomes. IL4I1 expression was assessed through 4D label-free proteomics, immunohistochemistry, and Western blotting. TCGA data were used to validate expression patterns and prognostic significance. Functional analyses were performed using IL4I1-knockout P53-mutant EC cell lines generated via CRISPR/Cas9, followed by phenotypic assays and xenograft models.Results: IL4I1 was significantly upregulated in deceased patients and correlated with immune microenvironment alterations in TCGA data. Knockout of IL4I1 inhibited proliferation, migration, and invasion in vitro and tumor growth in vivo.Conclusions: IL4I1 is a key player in the aggressiveness of P53-mutant EC. It holds promise as a prognostic biomarker and may serve as a novel target for precision therapies in this high-risk EC subtype.

摘要翻译： 

背景：子宫内膜癌（EC）是全球发病率持续上升的常见妇科恶性肿瘤之一。癌症基因组图谱（TCGA）将EC分为四种分子亚型，其中高拷贝数亚型以TP53突变为特征且预后不良，但该亚型的研究尚不充分。IL4I1作为一种参与多种癌症发展的免疫调节酶，已成为肿瘤进展的潜在生物标志物。本研究旨在探索IL4I1在P53突变型EC中的预后标志物价值，并评估其作为治疗靶点的潜力。 方法：我们回顾性分析了495例EC患者的临床资料，通过Sanger测序和免疫组化筛选出33例P53突变病例。采用激光捕获显微切割技术获取肿瘤组织，并按五年生存结局进行分层。通过4D非标记蛋白质组学、免疫组化和Western blotting评估IL4I1表达水平，并利用TCGA数据验证表达模式及预后意义。通过CRISPR/Cas9技术构建IL4I1敲除的P53突变EC细胞系，进行表型实验和异种移植模型的功能分析。 结果：IL4I1在死亡患者组织中显著上调，且与TCGA数据中免疫微环境改变相关。敲除IL4I1在体外抑制细胞增殖、迁移和侵袭能力，在体内抑制肿瘤生长。 结论：IL4I1是P53突变型EC侵袭性的关键调控因子，有望成为该高危EC亚型的预后生物标志物及精准治疗的新靶点。

原文链接：

Proteomic Identification of IL4I1 as a Therapeutic Target in P53-Mutant Endometrial Cancer