Exploration of Targeted Anti-tumor Therapy

Table 3. Univariate analysis of urinary microbiome parameters before and after BCG treatment and their association with OS, RFS, and PFS.

Parameters	Treatment of BCG	Group ratio	Univariate
			OS			RFS			PFS
			HR	95% CI	P-value	HR	95% CI	P-value	HR	95% CI	P-value
Bal_FB	Before	High/Low	1.23	0.85–2.04	0.34	1.32	0.85–2.04	0.22	1.28	0.81–2.03	0.3
Cory_nb	Before	High/Low	0.84	0.54–1.29	0.42	0.76	0.50–1.13	0.18	0.76	0.47–1.24	0.27
Entero_nb	Before	High/Low	1.12	0.73–1.72	0.59	0.91	0.60–1.38	0.66	1.37	0.81–2.30	0.24
Bal_inflam	Before	High/Low	1.08	0.74–1.58	0.69	0.97	0.69–1.37	0.87	1.2	0.80–1.79	0.38
Staph_nb	Before	High/Low	0.93	0.62–1.40	0.72	0.81	0.53–1.25	0.34	0.77	0.51–1.17	0.23
Bal_FB	After	High/Low	1.57	0.98–2.50	0.058	1.26	0.82–1.93	0.29	1.55	1.01–2.3	0.044
Cory_nb	After	High/Low	1.12	0.72–1.75	0.61	0.96	0.61–1.51	0.86	0.61	0.39–0.97	0.036
Entero_nb	After	High/Low	0.84	0.54–1.30	0.44	0.66	0.41–1.06	0.087	0.54	0.33–0.89	0.016
Bal_inflam	After	High/Low	1.24	0.69–2.20	0.47	1.3	0.73–2.31	0.37	1	0.60–1.66	0.99
Staph_nb	After	High/Low	1.19	0.77–1.83	0.44	1.06	0.69–1.64	0.78	1.25	0.81–1.93	0.32

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Hazard ratios (HRs) and 95% confidence intervals (CIs) from univariable Cox proportional hazards models evaluating the associations of urinary microbiome indices before and after BCG with overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). Each index was modeled as a continuous variable, and HRs represent the change in event hazard associated with a 1-unit increase in the transformed value. Bal_ denotes log-ratio balances between two taxonomic groups, and _nb denotes the log-abundance of a specific taxon. Bal_inflam = log[P/(F + B)]. P: Proteobacteria; F: Firmicutes; B: Bacteroidetes; Cory: Corynebacterium; Staph: Staphylococcus; Entero: Enterobacteriaceae.

Supplementary materials

The supplementary figures for this article are available at: https://www.explorationpub.com/uploads/Article/file/1002365_sup_1.pdf. The supplementary tables for this article are available at: https://www.explorationpub.com/uploads/Article/file/1002365_sup_2.xlsx.

Declarations

Acknowledgments

We thank the patients who participated in this study. We also thank Sayuri Onishi and Mariko Yoshimura (Department of Urology, Nara Medical University, Nara, Japan) for their technical assistance. The authors are responsible for obtaining permission from the acknowledged individuals and institutions.

Author contributions

YO: Conceptualization, Methodology, Investigation, Data curation, Formal analysis, Visualization, Writing—original draft, Writing—review & editing. MM: Conceptualization, Methodology, Investigation, Data curation, Formal analysis, Writing—review & editing, Funding acquisition. NN, TS, TO, KI, YN: Data curation, Writing—review & editing. NT, KF: Supervision, Data curation, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Yuki Oda and Makito Miyake, who are the Guest Editors of Exploration of Targeted Anti-tumor Therapy, had no involvement in the decision-making or review process of this manuscript. The other authors declare no conflicts of interest.

Ethical approval

The study was approved by the Nara Medical University Ethics Committee (No. 3698).

Consent to participate

Written informed consent to participate in the study was obtained from all participants.

Consent to publication

Written informed consent for publication of de-identified data was obtained from all participants.

Availability of data and materials

Raw 16S rRNA gene sequencing reads have been deposited in the NCBI Sequence Read Archive (SRA) under BioProject PRJNA1413953. Other datasets generated for this study are available from the corresponding author on reasonable request.

Funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number 23K08720 to Makito Miyake). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

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