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三阴性乳腺癌的瘤内微生物群落分析及相关代谢物变化

Intra-tumoral microbial community profiling and associated metabolites alterations of TNBC.

作者信息

Wang Yi, Qu Dingding, Zhang Yali, Jin Yiping, Feng Yu, Zhang He, Xia Qingxin

机构信息

Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.

Henan Medical Key Laboratory of Tumor Pathology and Artificial Intelligence Diagnosis, Zhengzhou, China.

出版信息

Front Oncol. 2023 Oct 12;13:1143163. doi: 10.3389/fonc.2023.1143163. eCollection 2023.

Abstract

Triple-negative breast cancer (TNBC) presents significant challenges to female health owing to the lack of therapeutic targets and its poor prognosis. In recent years, in the field of molecular pathology, there has been a growing focus on the role of intra-tumoral microbial communities and metabolic alterations in tumor cells. However, the precise mechanism through which microbiota and their metabolites influence TNBC remains unclear and warrants further investigation. In this study, we analyzed the microbial community composition in various subtypes of breast cancer through 16S rRNA MiSeq sequencing of formalin-fixed, paraffin-embedded (FFPE) tissue samples. Notably, , a microbe associated with cancer response, exhibited a significantly higher abundance in TNBC. Similarly, mass spectrometry-based metabolomic analysis revealed substantial differences in specific metabolites, such as nutriacholic, pregnanetriol, and cortol. Furthermore, we observed significant correlations between the intra-tumoral microbiome, clinicopathological characteristics, and human epidermal growth factor receptor-2 expression(HER2). Three microbial taxa (, and ) were associated with tumor-infiltrating lymphocytes(TILs), which are indicative of antitumor immunity. This study creatively utilized FFPE tissue samples to assess intra-tumoral microbial communities and their related metabolic correlations, presenting avenues for the identification of novel diagnostic biomarkers, the development of therapeutic strategies, and the early clinical diagnosis of TNBC.

摘要

三阴性乳腺癌(TNBC)由于缺乏治疗靶点且预后较差,给女性健康带来了重大挑战。近年来,在分子病理学领域,人们越来越关注肿瘤内微生物群落的作用以及肿瘤细胞中的代谢改变。然而,微生物群及其代谢产物影响TNBC的确切机制仍不清楚,值得进一步研究。在本研究中,我们通过对福尔马林固定、石蜡包埋(FFPE)组织样本进行16S rRNA MiSeq测序,分析了乳腺癌各亚型中的微生物群落组成。值得注意的是,一种与癌症反应相关的微生物在TNBC中的丰度显著更高。同样,基于质谱的代谢组学分析揭示了特定代谢物(如牛磺胆酸、孕三醇和皮质醇)的显著差异。此外,我们观察到肿瘤内微生物群、临床病理特征与人类表皮生长因子受体2表达(HER2)之间存在显著相关性。三种微生物分类群(、和)与肿瘤浸润淋巴细胞(TILs)相关,TILs是抗肿瘤免疫的指标。本研究创造性地利用FFPE组织样本评估肿瘤内微生物群落及其相关代谢相关性,为鉴定新型诊断生物标志物、制定治疗策略以及TNBC的早期临床诊断提供了途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f0a/10602718/f08d8af73a18/fonc-13-1143163-g001.jpg

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