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.
针对已知进展状态的巴雷特食管（BE）患者，其微环境特征如何影响BE向食管腺癌（EAC）进展的研究尚不充分，这既阻碍了对疾病进展机制的生物学理解，也限制了新型诊断与治疗方法的开发。本研究旨在探讨能否利用NanoString GeoMx数字空间分析平台，在内镜获取的福尔马林固定石蜡包埋（FFPE）样本上实现高度多元化的微环境检测，并初步识别可能介导BE进展的免疫细胞类型及相关通路。我们通过对两组患者的FFPE内镜活检样本进行空间蛋白质组学分析，检测了微环境及上皮细胞中49种蛋白的表达情况：一组为后期进展为高级别不典型增生或EAC的非不典型增生BE患者（n=7），另一组为随访至少5年未进展的患者（n=8）。随后，我们对三例包含BE区域、不典型增生区域及EAC区域的内镜黏膜切除样本进行了1812个癌症相关转录本的RNA分析。GeoMx DSP分析显示数据质量可靠，并成功检测到上皮与间质之间的预期差异。研究发现，与未进展者相比，进展者的非不典型增生BE活检样本中多种蛋白表达升高，这表明有必要开展进一步深入研究。
肿瘤(癌症)患者之家