胃腺体神经内分泌混合癌中神经内分泌癌和腺癌成分的不同表型和微环境特征。

IF 7.1 1区 医学 Q1 PATHOLOGY
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引用次数: 0

摘要

本研究旨在深入研究胃神经内分泌癌(NEC)和腺神经内分泌混合癌(MANEC)的基因表达和微环境特征。研究人员使用数字空间谱分析技术(GeoMx® DSP)分析了55例胃MANEC(32例)或NEC(23例)患者的组织芯片。从 MANEC 核心的腺癌部分(ADC-MANEC)和神经内分泌癌部分(NEC-MANEC)以及纯 NEC(pNEC)核心中选取了具有代表性的感兴趣区(ROI)。利用 GeoMx® 平台的屏蔽程序将所有 ROI 分成上皮成分和基质成分,然后进行转录组分析。对 ADC-MANEC 和 NEC-MANEC/pNEC 的基因表达进行比较,发现了上皮(包括 PEG10、MAP1B、STMN3 和 AKT3)和基质(FN1、COL1A1、SPARC 和 BGN)成分中几个表达不同的基因。基因组富集分析表明,与 E2F 靶点和 G2M 检查点相关的通路在 NEC-MANEC 和 pNEC 中的富集程度高于 ADC-MANEC。解卷积分析表明,微环境特征随组织学分化而变化。在 ADC-MANEC 中,上皮内浸润的免疫细胞相对较多,而在 NEC-MANEC 和 pNEC 中,基质中的成纤维细胞更多。这项研究利用 DSP 平台证实,MANEC 的每种组织学成分都有不同的表达谱,这取决于肿瘤与基质的分区。虽然 MANEC 的每种成分都有相同的基因来源,但在管理 MANEC 患者时不应忽视其独特的表型。这项研究为今后的研究提供了有用的验证数据集。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Distinctive Phenotypic and Microenvironmental Characteristics of Neuroendocrine Carcinoma and Adenocarcinoma Components in Gastric Mixed Adenoneuroendocrine Carcinoma

This study aimed to conduct an in-depth examination of gene expression and microenvironmental profiles of gastric neuroendocrine carcinoma (NEC) and mixed adeno-NEC (MANEC). Tissue microarrays from 55 patients with gastric MANEC (N = 32) or NEC (N = 23) were analyzed using digital spatial profiling (GeoMx DSP, NanoString Technologies). Representative regions of interest were selected from the adenocarcinoma (ADC) portion (ADC-MANEC) and the NEC portion (NEC-MANEC) of the MANEC cores, and pure NEC (pNEC) cores. All regions of interest were separated into epithelial components and stromal components using the masking procedure in the GeoMx platform, followed by transcriptome analysis. Comparison of gene expression between ADC-MANEC and NEC-MANEC/pNEC identified several differentially expressed genes in the epithelial (including PEG10, MAP1B, STMN3, and AKT3) and stromal (FN1, COL1A1, SPARC, and BGN) components. Gene set enrichment analysis revealed that pathways related to the E2F target and G2M checkpoint were more enriched in NEC-MANEC and pNEC than in ADC-MANEC. Deconvolution analysis showed that the microenvironmental profile varied according to histologic differentiation. In ADC-MANEC, intraepithelial infiltrating immune cells were relatively more numerous, whereas fibroblasts in the stroma were more abundant in NEC-MANEC and pNEC. This study confirmed the distinct expression profile of each histologic component of MANEC according to its tumor vs stromal compartment using the DSP platform. Although each component of MANEC shares the same genetic origin, distinctive phenotypes should not be overlooked when managing patients with MANEC. This study provides a useful validation data set for future studies.

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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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