Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA.
Department of Biochemistry and Molecular Biology, Next Generation Sequencing Core, The University of Texas Medical Branch, Galveston, TX.
Urol Oncol. 2022 Sep;40(9):410.e19-410.e27. doi: 10.1016/j.urolonc.2022.04.013. Epub 2022 May 23.
We sought to determine whether differences in subtype distribution and differentially expressed genes exist between African Americans (AAs) and European Americans (EAs) in patients with high-risk nonmuscle-invasive bladder cancer (NMIBC).
We performed a retrospective cohort study including 26 patients (14 AAs and 12 EAs) from the University of Texas Medical Branch and the Durham Veterans Affair Health Care System from 2010 to 2020 among treatment naïve, high-risk NMIBC. Profiled gene expressions were performed using the UROMOL classification system.
UROMOL racial subtype distributions were similar with class 2a being most common with 10 genes commonly upregulated in AAs compared to EAs including EFEMP1, S100A16, and MCL1 which are associated with progression to muscle-invasive bladder cancer, mitomycin C resistance, and bacillus Calmette-Guérin durability, respectively. We used single nuclei analysis to map the malignant cell heterogeneity in urothelial cancer which 5 distinct malignant epithelial subtypes whose presence has been associated with different therapeutic response prediction abilities. We mapped the expression of the 10 genes commonly upregulated by race as a function of the 5 malignant subtypes. This showed borderline (P = 0.056) difference among the subtypes suggesting AAs and EAs may be expected to have different therapeutic responses to treatments for bladder cancer. AAs were enriched with immune-related, inflammatory, and cellular regulation pathways compared to EAs, yet appeared to have reduced levels of the aggressive C3/CDH12 bladder tumor cell population.
While premature, gene expression differed between AAs and EAs, supporting potential race-based etiologies for muscle-invasion, response to treatments, and transcriptome pathway regulations.
我们旨在确定在患有高危非肌肉浸润性膀胱癌（NMIBC）的患者中，非裔美国人（AA）和欧洲裔美国人（EA）之间是否存在亚型分布和差异表达基因的差异。
我们进行了一项回顾性队列研究，纳入了 2010 年至 2020 年期间来自德克萨斯大学医学分校和达勒姆退伍军人事务医疗保健系统的 26 名治疗初治高危 NMIBC 患者（14 名 AA 和 12 名 EA）。使用 UROMOL 分类系统进行基因表达谱分析。
UROMOL 种族亚型分布相似，最常见的是 2a 类，与 EA 相比，AA 中有 10 个基因普遍上调，包括 EFEMP1、S100A16 和 MCL1，这些基因与进展为肌肉浸润性膀胱癌、丝裂霉素 C 耐药和卡介苗耐久性相关。我们使用单核细胞分析来绘制尿路上皮癌的恶性细胞异质性，发现了 5 种不同的恶性上皮亚型，其存在与不同的治疗反应预测能力相关。我们将种族普遍上调的 10 个基因的表达作为 5 种恶性亚型的函数进行了映射。这表明在亚型之间存在边缘差异（P=0.056），表明 AA 和 EA 可能对膀胱癌的治疗有不同的治疗反应。与 EA 相比，AA 富集了与免疫、炎症和细胞调节相关的途径，但似乎具有较低水平的侵袭性 C3/CDH12 膀胱肿瘤细胞群。
尽管还为时过早，但 AA 和 EA 之间的基因表达存在差异，支持肌肉浸润、对治疗的反应和转录组途径调节的潜在种族病因。
