PDF(Pubmed)
Abstract：
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 (n = 7) or from patients who, after at least 5 years follow-up, did not (n = 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.
摘要：
具有已知进展状态的患者的Barrett食管（BE）微环境的表征，为了确定它如何影响BE进展为食管腺癌（EAC），研究不足,阻碍了对进展的生物学理解以及新型诊断和疗法的发展。本研究的目的是确定是否可以在福尔马林固定的内镜下进行微环境的高度多重询问，石蜡包埋（FFPE）样品，利用NanoStringGeoMx数字空间分析（GeoMxDSP）平台，如果它可以开始识别可能介导BE进展的免疫细胞和途径的类型。我们对FFPE内窥镜活检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，这些蛋白质来自非增生性BE（NDBE）患者，后来发展为高度异型增生或EAC（n=7）或来自以下患者：经过至少5年的随访，没有（n=8）。然后，我们对包含BE区域的三个内窥镜粘膜切除术中的1812个癌症相关转录本进行了RNA分析，发育不良,和EAC。用GeoMxDSP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。与非进展者相比，发现几种蛋白质在进展者的NDBE活检中表达增加，建议进一步的研究是必要的。
