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乳腺微生物群与乳腺肿瘤特征及新辅助化疗的关联:一项病例对照研究。

Breast microbiome associations with breast tumor characteristics and neoadjuvant chemotherapy: A case-control study.

作者信息

Li Xuejun, Sun Xiaohu, Zhang Ai, Pang Jing, Li Yun, Yan Mengfan, Xu Zhen, Yu Yue, Yang Zhengjun, Chen Xi, Wang Xin, Cao Xu-Chen, Tang Nai-Jun

机构信息

Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China.

Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China.

出版信息

Front Oncol. 2022 Sep 12;12:926920. doi: 10.3389/fonc.2022.926920. eCollection 2022.

Abstract

BACKGROUND

Commensal microbiota have been proven to colonize the mammary gland, but whether their composition is altered in patients with breast cancer (BC) remains elusive. This study intends to explore the breast microbiome differences between benign and malignant diseases and to investigate the impact of neoadjuvant chemotherapy (NAC) on the breast microbiota in patients with BC.

METHODS

Breast normal adipose tissues (NATs) were collected from 79 patients with BC and 15 controls between July 2019 and November 2021. The BC group consisted of 29 patients who had received NAC and 50 who were non-NAC patients. Participants diagnosed with benign breast disease were recruited as controls. 16S rRNA gene sequencing was used to analyze the bacterial diversity of NATs.

RESULTS

The community structure of the NAT microbiome was significantly different between the BC and control groups. decreased (47.40% versus 39.74%), whereas increased (15.71% versus 25.33%) in patients with BC when compared with that in control tissues. Nine genera were enriched in BC NATs, and four genera levels increased in the control group. The associations between differential bacterial genera and breast tumor grade were calculated by Spearman's correlation. The results showed that tumor grade was positively associated with the relative abundance of and negatively related to , , , and . Moreover, menopause was associated with the microbiota composition change of non-NAC BC patients and related to the significant reduction in the abundance level of , , and . In addition, NAC was related to the beta diversity of patients with BC and associated with the decrease of and in postmenopausal patients. Of note, Tax4Fun functional prediction analysis revealed that the metabolic state was more exuberant in the BC group with upregulating of multiple metabolism-related pathways.

CONCLUSION

Our results offer new insight into the relationship between NAC and breast microbiota and help to better characterize the breast microbial dysbiosis that occurs in patients with BC. Further epidemiological studies with larger sample size and well-designed animal experiments are required to elucidate the role of breast microbiota in the therapeutic outcome of BC.

摘要

背景

共生微生物群已被证明可定殖于乳腺,但乳腺癌(BC)患者其组成是否改变仍不清楚。本研究旨在探讨良性和恶性疾病之间的乳腺微生物组差异,并研究新辅助化疗(NAC)对BC患者乳腺微生物群的影响。

方法

在2019年7月至2021年11月期间,从79例BC患者和15名对照者中收集乳腺正常脂肪组织(NATs)。BC组包括29例接受NAC的患者和50例未接受NAC的患者。招募被诊断为良性乳腺疾病的参与者作为对照。采用16S rRNA基因测序分析NATs的细菌多样性。

结果

BC组和对照组之间NAT微生物组的群落结构存在显著差异。与对照组织相比,BC患者中 减少(47.40%对39.74%),而 增加(15.71%对25.33%)。9个菌属在BC的NATs中富集,4个菌属在对照组中水平升高。通过Spearman相关性计算差异细菌属与乳腺肿瘤分级之间的关联。结果显示,肿瘤分级与 的相对丰度呈正相关,与 、 、 和 呈负相关。此外,绝经与未接受NAC的BC患者的微生物群组成变化有关,并且与 、 和 的丰度水平显著降低有关。此外,NAC与BC患者的β多样性有关,并且与绝经后患者中 和 的减少有关。值得注意的是,Tax4Fun功能预测分析显示,BC组中多种代谢相关途径上调,代谢状态更为旺盛。

结论

我们的结果为NAC与乳腺微生物群之间的关系提供了新的见解,并有助于更好地表征BC患者中发生的乳腺微生物失调。需要进一步开展更大样本量的流行病学研究和设计良好的动物实验,以阐明乳腺微生物群在BC治疗结果中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f256/9510588/e4326c160dfb/fonc-12-926920-g001.jpg

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