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

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 bacter...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Heliyon
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023070081
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author 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
author_facet 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
author_sort Toshihiro Uemura
collection DOAJ
description 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.
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spelling doaj.art-773d78540e4440d9b22b02288d314b512023-10-01T06:01:19ZengElsevierHeliyon2405-84402023-09-0199e19800Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinomaToshihiro Uemura0Atsunari Kawashima1Kentaro Jingushi2Daisuke Motooka3Takuro Saito4Sassi Nesrine5Toshiki Oka6Yohei Okuda7Akinaru Yamamoto8Gaku Yamamichi9Eisuke Tomiyama10Yu Ishizuya11Yoshiyuki Yamamoto12Taigo Kato13Koji Hatano14Kazutake Tsujikawa15Hisashi Wada16Norio Nonomura17Department of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Corresponding author.Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Infection Metagenomics, Genome Information Research Center, Osaka University Research Institute for Microbial Diseases, Suita, Osaka, 565-0871, JapanDepartment 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, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanLaboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, JapanDepartment of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, JapanDepartment of Urology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, JapanThis 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.http://www.sciencedirect.com/science/article/pii/S2405844023070081
spellingShingle 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
Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinoma
Heliyon
title Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinoma
title_full Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinoma
title_fullStr Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinoma
title_full_unstemmed Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinoma
title_short Bacteria-derived DNA in serum extracellular vesicles are biomarkers for renal cell carcinoma
title_sort bacteria derived dna in serum extracellular vesicles are biomarkers for renal cell carcinoma
url http://www.sciencedirect.com/science/article/pii/S2405844023070081
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