The role of TERT C228T and KDM6A alterations and TME in NMIBC treated with BCG

IF 6.8 1区医学 Q1 ONCOLOGY

NPJ Precision Oncology Pub Date : 2024-10-01 DOI:10.1038/s41698-024-00725-4

Qi-Dong Xia, Jian-Xuan Sun, Zhi-Peng Yao, Jun-Lin Lu, Chen-Qian Liu, Jin-Zhou Xu, Ye An, Meng-Yao Xu, Si-Han Zhang, Xing-Yu Zhong, Na Zeng, Si-Yang Ma, Hao-Dong He, Heng-Long Hu, Jia Hu, Yi Lu, Bing Li, Yao-Bing Chen, Zheng Liu, Shao-Gang Wang

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Abstract

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette–Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment.

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TERT C228T和KDM6A改变及TME在卡介苗治疗的NMIBC中的作用

我们的目的是研究非肌浸润性膀胱癌（NMIBC）的基因组和肿瘤微环境（TME）特征，并探索高风险 NMIBC 患者（根据欧洲泌尿外科协会（EAU）的风险分层）对卡介苗（BCG）治疗反应的潜在预测标志物。研究人员回顾性地纳入了40名接受全切手术并注射卡介苗的高危NMIBC（cTis-T1N0M0）患者。手术样本接受了新一代测序（NGS）和多重免疫荧光（mIF）检测。基因组图谱分析显示，TERT（55%）、KDM6A（32.5%）、FGFR3（30%）、PIK3CA（30%）、TP53（27.5%）和ARID1A（20%）的改变发生率较高。TME分析显示，巨噬细胞、NK细胞、T细胞亚群在肿瘤和基质中的比例不同。多变量分析发现，TERT C228T和KDM6A的改变是与RFS较差相关的两个独立因素。该研究全面描述了NMIBC的基因组和TME特征，并确定了卡介苗治疗的潜在预测生物标志物。

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

NPJ Precision Oncology ONCOLOGY-

CiteScore

9.90

自引率

1.30%

发文量

审稿时长

18 weeks

期刊介绍： Online-only and open access, npj Precision Oncology is an international, peer-reviewed journal dedicated to showcasing cutting-edge scientific research in all facets of precision oncology, spanning from fundamental science to translational applications and clinical medicine.