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

doi:10.1016/j.heliyon.2023.e19800

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

Heliyon. 2023 Sep 6;9(9):e19800. doi: 10.1016/j.heliyon.2023.e19800. eCollection 2023 Sep.

Authors

Toshihiro Uemura¹, Atsunari Kawashima¹, Kentaro Jingushi², Daisuke Motooka³, Takuro Saito^{4

5}, Sassi Nesrine¹, Toshiki Oka¹, Yohei Okuda¹, Akinaru Yamamoto¹, Gaku Yamamichi¹, Eisuke Tomiyama¹, Yu Ishizuya¹, Yoshiyuki Yamamoto¹, Taigo Kato¹, Koji Hatano¹, Kazutake Tsujikawa², Hisashi Wada⁵, Norio Nonomura¹

Affiliations

¹ Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
² Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
³ Department of Infection Metagenomics, Genome Information Research Center, Osaka University Research Institute for Microbial Diseases, Suita, Osaka, 565-0871, Japan.
⁴ Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
⁵ Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.

Abstract

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.