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
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.
