Frei Nicola F, Khoshiwal Amir M, Stougie Pim, Odze Robert, Camilleri-Broet Sophie, Ferri Lorenzo, Duits Lucas C, Bergman Jacques, Stachler Matthew D
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Amsterdam UMC Locatie AMC, 1105 AZ Amsterdam, The Netherlands.
Cancers (Basel). 2023 Dec 18;15(24):5895. doi: 10.3390/cancers15245895.
Characterization of the Barrett's esophagus (BE) microenvironment in patients with a known progression status, to determine how it may influence BE progression to esophageal adenocarcinoma (EAC), has been understudied, hindering both the biological understanding of the progression and the development of novel diagnostics and therapies. This study's aim was to determine if a highly multiplex interrogation of the microenvironment can be performed on endoscopic formalin-fixed, paraffin-embedded (FFPE) samples, utilizing the NanoString GeoMx digital spatial profiling (GeoMx DSP) platform and if it can begin to identify the types of immune cells and pathways that may mediate the progression of BE. We performed a spatial proteomic analysis of 49 proteins expressed in the microenvironment and epithelial cells of FFPE endoscopic biopsies from patients with non-dysplastic BE (NDBE) who later progressed to high-grade dysplasia or EAC 7) or from patients who, after at least 5 years follow-up, did not = 8). We then performed an RNA analysis of 1812 cancer-related transcripts on three endoscopic mucosal resections containing regions of BE, dysplasia, and EAC. Profiling with GeoMx DSP showed reasonable quality metrics and detected expected differences between epithelium and stroma. Several proteins were found to have an increased expression within NDBE biopsies from progressors compared to non-progressors, suggesting further studies are warranted.
对已知进展状态的巴雷特食管(BE)患者的微环境进行表征,以确定其如何影响BE进展为食管腺癌(EAC),这方面的研究较少,阻碍了对该进展的生物学理解以及新型诊断和治疗方法的开发。本研究的目的是确定是否可以利用NanoString GeoMx数字空间分析(GeoMx DSP)平台,对内镜下福尔马林固定、石蜡包埋(FFPE)样本进行微环境的高度多重检测,以及是否能够开始识别可能介导BE进展的免疫细胞类型和通路。我们对后来进展为高级别异型增生或EAC的非异型增生性BE(NDBE)患者(n = 7)或至少随访5年后未进展的患者(n = 8)的FFPE内镜活检组织的微环境和上皮细胞中表达的49种蛋白质进行了空间蛋白质组学分析。然后,我们对包含BE、异型增生和EAC区域的三份内镜黏膜切除术样本进行了1812种癌症相关转录本的RNA分析。使用GeoMx DSP进行分析显示出合理的质量指标,并检测到上皮和基质之间的预期差异。与未进展者相比,进展者的NDBE活检组织中发现几种蛋白质的表达增加,这表明有必要进行进一步研究。