An exploratory study investigating the impact of the bladder tumor microbiome on Bacillus Calmette Guerin (BCG) response in non-muscle invasive bladder cancer

被引：3

作者：

Knorr, Jacob ^{[1
]}

Lone, Zaeem ^{[2
]}

Werneburg, Glenn ^{[1
]}

Adler, Ava ^{[3
]}

Agudelo, Jose ^{[3
]}

Suryavanshi, Mangesh ^{[3
]}

Campbell, Rebecca A. ^{[1
]}

Ericson, Kyle ^{[4
]}

Qiu, Hong ^{[3
]}

Bajic, Petar ^{[1
]}

Haber, Georges-Pascal ^{[1
]}

Weight, Christopher J. ^{[1
]}

Ahern, Philip P. ^{[3
]}

Almassi, Nima ^{[1
]}

Miller, Aaron W. ^{[1
,3
]}

Lee, Byron H. ^{[5
]}

机构：

[1] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA

[2] Cleveland Clin, Lerner Coll Med, Cleveland, OH USA

[3] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA

[4] Univeristy Hosp Dept Urol, Cleveland, OH USA

[5] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

来源：

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS | 2024年 / 42卷 / 09期

关键词：

Bladder cancer; BCG; Microbiome; TRANSURETHRAL RESECTION; METAANALYSIS; RECURRENCE; EXPRESSION; DATABASE; URINE;

D O I：

10.1016/j.urolonc.2024.04.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Intravesical Bacillus Calmette-Guerin (BCG) is standard of care for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC). The effect of the bladder microbiome on response to BCG is unclear. We sought to characterize the microbiome of bladder tumors in BCG-responders and non-responders and identify potential mechanisms that drive treatment response. Materials and methods: Patients with archival pre-treatment biopsy samples (2012-2018) were identified retrospectively. Prospectively, urine and fresh tumor samples were collected from individuals with high-risk NMIBC (2020-2023). BCG response was defined as tumor-free 2 years from induction therapy. Extracted DNA was sequenced for 16S rRNA and shotgun metagenomics. Primary outcomes were species richness (alpha-diversity) and microbial composition (beta-diversity). Paired t-tests were performed for alpha-diversity (Observed species/Margalef). Statistical analysis for beta-diversity (weighted and unweighted UniFrac distances, weighted Bray-Curtis dissimilarity) were conducted through Permanova, with 999 permutations. Results: Microbial species richness (P < 0.001) and composition (P = 0.001) differed between BCG responders and non-responders. Lactobacillus spp. were significantly enriched in BCG-responders. Shotgun metagenomics identified possible mechanistic pathways such as assimilatory sulfate reduction. Conclusion: A compositional difference exists in the tumor microbiome of BCG responders and non-responders with Lactobacillus having increased abundance in BCG responders.

引用

页码：291e1 / 291e11

页数：11

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