Wen Qin, Wang Shubin, Fu Shunlian, Zhou Xinxiang, Min Yalan, Lang Jinyi, Chen Meihua
School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
Front Oncol. 2025 Jun 12;15:1544786. doi: 10.3389/fonc.2025.1544786. eCollection 2025.
The intratumoral microbiota has attracted considerable interest in carcinogenesis, progression, and treatment owing to advancements in sequencing technology. This systematic review provides a comprehensive overview of the current literature regarding the diversity and compositional characteristics of the intratumoral microbiota in women's cancers. Additionally, it also explores potential associations among intratumoral microbiota, estrogen, and anti-tumor therapies.
A comprehensive literature search was conducted using PubMed, Embase, Web of Science, and the Cochrane Library from their inception to May 1, 2024. The review protocol was pre-registered in PROSPERO (CRD 42024601213). Articles were assessed utilizing the Newcastle-Ottawa Scale (NOS). To estimate the effect size and variability in microbial diversity changes, the standardized mean difference (SMD) and 95% confidence intervals (CIs) were employed. The systematic review adhered to PRISMA reporting guidelines, and meta-analyses were performed using Review Manager version 5.4.
This systematic review included 29 of 8,291 studies after a thorough screening process. Of the 22 studies investigating α-diversity in women's cancers, disease-free controls, and those with benign conditions, notable changes in diversity indices were observed. Compared to adjacent normal tissues, the Simpson index significantly decreased in breast cancer (SMD = -0.75, 95% CI: [-0.94, -0.55]) and endometrial cancer (SMD = -0.83, 95% CI: [-1.37, -0.28]). The Chao1 index was reduced in endometrial cancer tumor tissues relative to normal tissues (SMD = -2.25, 95% CI: [-3.13, -1.36]), while the Shannon index decreased in ovarian cancer tumor tissues (SMD = -0.61, 95% CI: [-1.18, -0.04]). In comparisons between tumor and benign tissues, the Chao1 index was decreased (SMD = -0.64, 95% CI: [-1.20, -0.08], I² = 0%), while the Simpson index was increased (SMD = 0.36, 95% CI: [0.01, 0.71], I² = 0%) in patients with ovarian cancer. Other microbial diversity indices showed no significant differences between tumor and non-tumor tissues. At the phylum level, were enriched in tumor tissues, while and predominated in non-tumor tissues. At the genus level, , , , , and were consistently more abundant in cancerous tissues. Microbial alterations were also linked to estrogen receptor (ER) status, with negatively correlated with ER status in two studies. Furthermore, one study on the effect of antineoplastic therapy indicated that neoadjuvant chemotherapy reduced microbial diversity in breast cancer patients (n = 15 vs. n = 18) (Shannon index: SMD = -0.95, 95% CI: [-1.68, -0.22]).
This study highlights significant differences in microbiota composition between tumor and non-tumor tissues in women's cancers, emphasizing changes in intratumoral microbiota influenced by estrogen and antineoplastic treatments. Further research is needed to explore the potential for developing targeted therapies based on estrogen-driven microbiota alterations. Investigations may yield insights into the enhancement of female reproductive health and the improvement of treatment efficacy for female cancers.
https://www.crd.york.ac.uk/PROSPERO/view/CRD42024601213, identifier CRD 42024601213.
由于测序技术的进步，肿瘤内微生物群在致癌、进展和治疗方面引起了相当大的关注。本系统评价全面概述了目前关于女性癌症肿瘤内微生物群的多样性和组成特征的文献。此外，还探讨了肿瘤内微生物群、雌激素和抗肿瘤治疗之间的潜在关联。
使用PubMed、Embase、Web of Science和Cochrane图书馆从其创建到2024年5月1日进行了全面的文献检索。该综述方案已在PROSPERO（CRD 42024601213）中预先注册。使用纽卡斯尔-渥太华量表（NOS）评估文章。为了估计微生物多样性变化的效应大小和变异性，采用了标准化平均差（SMD）和95%置信区间（CIs）。该系统评价遵循PRISMA报告指南，并使用Review Manager 5.4版进行荟萃分析。
经过全面筛选过程，本系统评价纳入了8291项研究中的29项。在22项调查女性癌症、无病对照和良性疾病患者α多样性的研究中，观察到多样性指数有显著变化。与相邻正常组织相比，乳腺癌（SMD = -0.75，95% CI：[-0.94，-0.55]）和子宫内膜癌（SMD = -0.83，95% CI：[-1.37，-0.28]）的辛普森指数显著降低。子宫内膜癌肿瘤组织相对于正常组织的Chao1指数降低（SMD = -2.25，95% CI：[-3.13，-1.36]），而卵巢癌肿瘤组织的香农指数降低（SMD = -0.61，95% CI：[-1.18，-0.04]）。在肿瘤组织与良性组织的比较中，卵巢癌患者的Chao1指数降低（SMD = -0.64，95% CI：[-1.20，-0.08]，I² = 0%），而辛普森指数升高（SMD = 0.36，95% CI：[0.01，0.71]，I² = 0%）。其他微生物多样性指数在肿瘤组织与非肿瘤组织之间无显著差异。在门水平上，[此处原文缺失具体内容]在肿瘤组织中富集，而[此处原文缺失具体内容]和[此处原文缺失具体内容]在非肿瘤组织中占主导地位。在属水平上，[此处原文缺失具体内容]、[此处原文缺失具体内容]、[此处原文缺失具体内容]、[此处原文缺失具体内容]和[此处原文缺失具体内容]在癌组织中始终更为丰富。微生物改变也与雌激素受体（ER）状态相关，在两项研究中[此处原文缺失具体内容]与ER状态呈负相关。此外，一项关于抗肿瘤治疗效果的研究表明，新辅助化疗降低了乳腺癌患者的微生物多样性（n = 15 vs. n = 18）（香农指数：SMD = -0.95，95% CI：[-1.68，-0.22]）。
本研究强调了女性癌症肿瘤组织与非肿瘤组织中微生物群组成的显著差异，强调了雌激素和抗肿瘤治疗对肿瘤内微生物群的影响。需要进一步研究探索基于雌激素驱动的微生物群改变开发靶向治疗的潜力。研究可能会为增强女性生殖健康和提高女性癌症治疗效果提供见解。
https://www.crd.york.ac.uk/PROSPERO/view/CRD42024601213，标识符CRD 42024601213。
