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GATA3/FOXA1共表达缺失预示上尿路尿路上皮癌预后不良。

Absence of GATA3/FOXA1 co-expression predicts poor prognosis in upper tract urothelial carcinoma.

作者信息

Wang Yue, Wang Yunfan, He Huiying, Xiong Yan

机构信息

Department of Pathology, Peking University First Hospital, Beijing, China.

Department of Pathology, Peking University Shougang Hospital, Beijing, China.

出版信息

Front Oncol. 2024 Feb 15;14:1302864. doi: 10.3389/fonc.2024.1302864. eCollection 2024.

DOI:10.3389/fonc.2024.1302864
PMID:38425344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10902436/
Abstract

OBJECTIVE

GATA binding protein 3 (GATA3) and forkhead box A1 (FOXA1) have been individually implicated in the progression of upper tract urothelial carcinoma (UTUC). This study aims to evaluate the prognostic value of GATA3/FOXA1 co-expression in UTUC patients.

METHODS

We collected 108 UTUC pathological tissue samples with complete follow-up data and 24 normal control urothelial tissues. We created a 132-site microarray and performed immunohistochemistry (IHC) to measure GATA3 and FOXA1 expression levels. Kaplan-Meier survival and Cox regression analyses were conducted to assess UTUC prognosis.

RESULTS

GATA3 expression was positively correlated with FOXA1 (P=0.031). Absence of GATA3/FOXA1 co-expression (GATA3-/FOXA1-) was associated with tumor extensive necrosis (P=0.001) after Bonferroni correction for multiple comparisons. GATA3-/FOXA1- was associated with shorter Disease-Free Survival (DFS) (P=0.001) and Cancer-Specific Survival (CSS) (P<0.001) than other combination groups. Multivariate analyses identified extensive necrosis as an independent prognostic factor for CSS (P=0.030).

CONCLUSIONS

Our study revealed a positive correlation between GATA3 and FOXA1 expression in UTUC. GATA3-/FOXA1- is linked to tumor extensive necrosis and poor prognosis in UTUC and may serve as a potential biomarker for UTUC patients.

摘要

目的

GATA结合蛋白3（GATA3）和叉头框A1（FOXA1）分别与上尿路尿路上皮癌（UTUC）的进展有关。本研究旨在评估GATA3/FOXA1共表达在上尿路尿路上皮癌患者中的预后价值。

方法

我们收集了108例具有完整随访数据的上尿路尿路上皮癌病理组织样本和24例正常对照尿路上皮组织。我们制作了一个包含132个位点的微阵列，并进行免疫组织化学（IHC）检测以测量GATA3和FOXA1的表达水平。进行Kaplan-Meier生存分析和Cox回归分析以评估上尿路尿路上皮癌的预后。

结果

GATA3表达与FOXA1呈正相关（P = 0.031）。在进行多重比较的Bonferroni校正后，GATA3/FOXA1共表达缺失（GATA3-/FOXA1-）与肿瘤广泛坏死相关（P = 0.001）。与其他组合组相比，GATA3-/FOXA1-与无病生存期（DFS）缩短（P = 0.001）和癌症特异性生存期（CSS）缩短（P < 0.001）相关。多变量分析确定广泛坏死是CSS的独立预后因素（P = 0.030）。

结论

我们的研究揭示了上尿路尿路上皮癌中GATA3和FOXA1表达之间的正相关。GATA3-/FOXA1-与上尿路尿路上皮癌的肿瘤广泛坏死和不良预后相关，可能作为上尿路尿路上皮癌患者的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/687a/10902436/1219ea5616d5/fonc-14-1302864-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/687a/10902436/dac3be0ac194/fonc-14-1302864-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/687a/10902436/1219ea5616d5/fonc-14-1302864-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/687a/10902436/dac3be0ac194/fonc-14-1302864-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/687a/10902436/1219ea5616d5/fonc-14-1302864-g002.jpg

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本文引用的文献

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European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update.欧洲泌尿外科学会上尿路尿路上皮癌指南：2023 年更新版。
Eur Urol. 2023 Jul;84(1):49-64. doi: 10.1016/j.eururo.2023.03.013. Epub 2023 Mar 24.
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Comprehensive genomic profiling of upper tract urothelial carcinoma and urothelial carcinoma of the bladder identifies distinct molecular characterizations with potential implications for targeted therapy & immunotherapy.全面的上尿路尿路上皮癌和膀胱尿路上皮癌基因组分析确定了具有潜在靶向治疗和免疫治疗意义的不同分子特征。
Front Immunol. 2023 Feb 3;13:1097730. doi: 10.3389/fimmu.2022.1097730. eCollection 2022.
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FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation.
FOXA1抑制作用驱动具有鳞状分化的膀胱癌中的谱系可塑性和免疫异质性。
Nat Commun. 2022 Nov 2;13(1):6575. doi: 10.1038/s41467-022-34251-3.
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GATA3 expression loss is linked to stage progression but is unrelated to prognosis in muscle-invasive urothelial carcinoma of the bladder.GATA3 表达缺失与分期进展相关，但与肌层浸润性膀胱癌的预后无关。
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The estrogen receptor/GATA3/FOXA1 transcriptional network: lessons learned from breast cancer.雌激素受体/GATA3/FOXA1 转录网络：从乳腺癌中得到的启示。
Curr Opin Struct Biol. 2021 Dec;71:65-70. doi: 10.1016/j.sbi.2021.05.015. Epub 2021 Jul 2.
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