文章：

早期（非转移性）与原发性转移性管腔型乳腺肿瘤在肿瘤分子及微环境景观上的差异

Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors

原文发布日期：30 August 2023

DOI: 10.3390/cancers15174341

类型: Article

开放获取: 是

英文摘要：

Background:The molecular mechanisms underlying the de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown.Materials and Methods:Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/−, HER2−), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical–pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n = 32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 × 10 µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR; deconvolution was performed using CIBERSORTx to assess immune cell fractions. A paired Wilcoxon test was used to compare dnMBC and eBC groups and corrected for the false discovery rate.Results:Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that theCCL17and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group.Conclusions:Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients.

摘要翻译： 

背景：管腔型乳腺癌新发转移（dnMBC）的分子机制在很大程度上仍不明确。材料与方法：从临床病理数据库中筛选出新诊断的dnMBC患者（2/3级，ER+，PR+/−，HER2−），这些患者均具备取自原发肿瘤的空芯针穿刺活检（CNB）样本。将dnMBC患者的肿瘤与新诊断且基线时无远处转移患者（eBC组）的肿瘤进行1:1配对匹配（n=32）。从福尔马林固定石蜡包埋（FFPE）CNB样本的5×10µm切片中提取RNA，使用Illumina平台进行RNA测序。采用EdgeR评估差异表达基因（DEG），使用CIBERSORTx进行反卷积分析以评估免疫细胞组分。采用配对Wilcoxon检验比较dnMBC组与eBC组，并对错误发现率进行校正。结果：与eBC组相比，dnMBC组中许多调控性DEG显著下调。同时，免疫相关和缺氧相关特征显著上调。配对Wilcoxon分析显示，dnMBC组中CCL17和中性粒细胞组分显著上调，而记忆B细胞组分显著下调。结论：与eBC患者的同类肿瘤相比，dnMBC患者的原发管腔型肿瘤在转录组学和免疫学方面存在显著差异。

原文链接：

Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors