PO.CL05.07 · 临床研究
卵巢癌中的FOXA1：治疗靶点与免疫治疗增强剂
FOXA1 in ovarian cancer: Therapeutic target and immunotherapy enhancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
目的
本研究旨在阐明FOXA1(Forkhead Box A1)在卵巢癌中的致癌作用，并评估其作为治疗靶点和诊断生物标志物的潜力。我们进一步研究了抑制FOXA1是否能增强对免疫检查点阻断的应答性并克服化疗耐药。
方法
共分析了76份卵巢组织样本，包括9份正常、34份良性和33份恶性标本。进行免疫组织化学(IHC)染色以评估FOXA1表达及其与肿瘤分期的相关性。在SK-OV3和HEYA8细胞系中使用FOXA1 siRNA进行功能研究。评估FOXA1沉默后细胞增殖、迁移、侵袭和划痕愈合能力的变化。采用定量RT-PCR测定FOXA1及上皮-间质转化(EMT)相关基因的表达。此外，评估了抑制FOXA1对卡铂和免疫检查点抑制剂atezolizumab敏感性的影响。
结果
IHC分析显示，正常、良性和恶性组织之间FOXA1表达存在显著差异，且表达水平与肿瘤分期相关。FOXA1沉默显著降低了细胞增殖，并使迁移和侵袭减少60-80%。FOXA1敲低后EMT相关基因明显下调。此外，抑制FOXA1增强了卵巢癌细胞对atezolizumab的应答性并降低了卡铂耐药。
结论
FOXA1在卵巢癌中作为致癌驱动因子，促进增殖、侵袭和EMT激活。其过表达与疾病进展相关，支持其作为诊断和预后生物标志物的作用。靶向FOXA1可能增强免疫治疗疗效并克服卵巢癌的化疗耐药。
查看英文原文 English abstract
OBJECTIVE
This study aimed to elucidate the oncogenic role of FOXA1 (Forkhead Box A1) in ovarian cancer and to evaluate its potential as both a therapeutic target and a diagnostic biomarker. We further investigated whether FOXA1 inhibition could enhance responsiveness to immune checkpoint blockade and overcome chemoresistance.
METHODS
A total of 76 ovarian tissue samples were analyzed, including 9 normal, 34 benign, and 33 malignant specimens. Immunohistochemical (IHC) staining was performed to assess FOXA1 expression and its correlation with tumor stage. Functional studies were conducted using FOXA1 siRNA in SK-OV3 and HEYA8 cell lines. Changes in cell proliferation, migration, invasion, and wound-healing ability were evaluated following FOXA1 silencing. Quantitative RT-PCR was used to measure FOXA1 and epithelial-mesenchymal transition (EMT)-related gene expression. In addition, the effects of FOXA1 inhibition on sensitivity to carboplatin and the immune checkpoint inhibitor atezolizumab were assessed.
RESULTS
IHC analysis revealed significant differences in FOXA1 expression among normal, benign, and malignant tissues, with expression levels correlating with tumor stage. FOXA1 silencing significantly reduced cell proliferation and decreased migration and invasion by 60-80%. EMT-related genes were markedly downregulated after FOXA1 knockdown. Moreover, FOXA1 inhibition enhanced atezolizumab responsiveness and reduced carboplatin resistance in ovarian cancer cells.
CONCLUSION
FOXA1 acts as an oncogenic driver in ovarian cancer, promoting proliferation, invasion, and EMT activation. Its overexpression correlates with disease progression, supporting its role as a diagnostic and prognostic biomarker. Targeting FOXA1 may enhance immunotherapy efficacy and overcome chemoresistance in ovarian cancer.
利益披露 Disclosure
S. Jeon, None.