Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinoma

Toshihiro Uemura; Atsunari Kawashima; Kentaro Jingushi; Daisuke Motooka; Takuro Saito; Sassi Nesrine; Toshiki Oka; Yohei Okuda; Akinaru Yamamoto; Gaku Yamamichi; Eisuke Tomiyama; Yu Ishizuya; Yoshiyuki Yamamoto; Taigo Kato; Koji Hatano; Kazutake Tsujikawa; Hisashi Wada; Norio Nonomura

Heliyon (Sep 2023)

Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinoma

Toshihiro Uemura,
Atsunari Kawashima,
Kentaro Jingushi,
Daisuke Motooka,
Takuro Saito,
Sassi Nesrine,
Toshiki Oka,
Yohei Okuda,
Akinaru Yamamoto,
Gaku Yamamichi,
Eisuke Tomiyama,
Yu Ishizuya,
Yoshiyuki Yamamoto,
Taigo Kato,
Koji Hatano,
Kazutake Tsujikawa,
Hisashi Wada,
Norio Nonomura

Affiliations

Toshihiro Uemura: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Atsunari Kawashima: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Corresponding author.
Kentaro Jingushi: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan
Daisuke Motooka: Department of Infection Metagenomics, Genome Information Research Center, Osaka University Research Institute for Microbial Diseases, Suita, Osaka, 565-0871, Japan
Takuro Saito: Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan; Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
Sassi Nesrine: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Toshiki Oka: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Yohei Okuda: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Akinaru Yamamoto: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Gaku Yamamichi: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Eisuke Tomiyama: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Yu Ishizuya: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Yoshiyuki Yamamoto: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Taigo Kato: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Koji Hatano: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
Kazutake Tsujikawa: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan
Hisashi Wada: Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
Norio Nonomura: Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

Journal volume & issue: Vol. 9, no. 9
p. e19800

Abstract

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This is the first study to determine the clinical importance of circulating bacterial DNA in patients with renal cell carcinoma (RCC). We performed 16S rRNA metagenomic analysis of serum extracellular vesicles (EVs) from 88 patients with RCC and 10 healthy donors and identified three abundant bacterial DNA: Bacteroidia, TM7-1, and Sphingomonadales. Combining characteristic bacterial DNA information (three bacteria-derived DNA), a BTS index was created to diagnose patients with RCC. The BTS index showed high sensitivity not only in the discovery cohort, but also in the validation cohort, suggesting that it was useful as a screening test. Furthermore, in nivolumab treatment of RCC, patients with higher levels of Bacteroidia DNA in serum EVs had significantly poorer progression-free and overall survival than did those with lower levels. This study showed that circulating Bacteria-derived DNA could be used as a biomarker for RCC.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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