Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level

Abstract Identifying a novel method to monitor metastatic bladder cancer status at the cell-gene level could lead to earlier appropriate therapeutic intervention and better outcomes. In this study, we evaluated a practical method to monitor the cancer status at the circulating cell-gene level before...

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Main Authors: Ryota Ogura, Saya Ito, Takashi Ueda, Yusuke Gabata, Satoshi Sako, Yuta Inoue, Takeshi Yamada, Hirotaka Konishi, Atsuko Fujihara, Osamu Ukimura
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-46977-1
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author Ryota Ogura
Saya Ito
Takashi Ueda
Yusuke Gabata
Satoshi Sako
Yuta Inoue
Takeshi Yamada
Hirotaka Konishi
Atsuko Fujihara
Osamu Ukimura
author_facet Ryota Ogura
Saya Ito
Takashi Ueda
Yusuke Gabata
Satoshi Sako
Yuta Inoue
Takeshi Yamada
Hirotaka Konishi
Atsuko Fujihara
Osamu Ukimura
author_sort Ryota Ogura
collection DOAJ
description Abstract Identifying a novel method to monitor metastatic bladder cancer status at the cell-gene level could lead to earlier appropriate therapeutic intervention and better outcomes. In this study, we evaluated a practical method to monitor the cancer status at the circulating cell-gene level before and after treatment in fourteen patients with metastatic bladder cancer who were indicated for systemic drug therapy. Patients were assessed via imaging before and after drug treatment, and cell-free DNA (cfDNA) analysis was performed to detect three parameters: cfDNA level, ERRB2 gene copy numbers, and telomerase reverse transcriptase (TERT) gene mutations. We hypothesized that decreased cfDNA levels, a normal copy number of ERB-B2 receptor tyrosine kinase 2 (ERBB2), and the absence of the TERT C228T mutation indicate cancer suppression. We found that a > 1.8-fold increase in cfDNA levels, increased copy number of ERBB2, or the existence of the TERT C228T mutation indicated disease progression. Stable cfDNA levels, normal ERBB2 copy number, and the absence of TERT C228T mutations indicate a stable cancer status. Collectively, our results show that the combination of cfDNA concentration, TERT mutation, and ERBB2 copy number may be useful for determining the efficacy of drug therapy in patients with metastatic bladder cancer.
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spelling doaj.art-b7c7a2d06b1c4da793cda991c69452ad2023-12-17T12:17:28ZengNature PortfolioScientific Reports2045-23222023-11-011311910.1038/s41598-023-46977-1Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene levelRyota Ogura0Saya Ito1Takashi Ueda2Yusuke Gabata3Satoshi Sako4Yuta Inoue5Takeshi Yamada6Hirotaka Konishi7Atsuko Fujihara8Osamu Ukimura9Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDivision of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of MedicineDepartment of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineDepartment of Urology, Graduate School of Medical Science, Kyoto Prefectural University of MedicineAbstract Identifying a novel method to monitor metastatic bladder cancer status at the cell-gene level could lead to earlier appropriate therapeutic intervention and better outcomes. In this study, we evaluated a practical method to monitor the cancer status at the circulating cell-gene level before and after treatment in fourteen patients with metastatic bladder cancer who were indicated for systemic drug therapy. Patients were assessed via imaging before and after drug treatment, and cell-free DNA (cfDNA) analysis was performed to detect three parameters: cfDNA level, ERRB2 gene copy numbers, and telomerase reverse transcriptase (TERT) gene mutations. We hypothesized that decreased cfDNA levels, a normal copy number of ERB-B2 receptor tyrosine kinase 2 (ERBB2), and the absence of the TERT C228T mutation indicate cancer suppression. We found that a > 1.8-fold increase in cfDNA levels, increased copy number of ERBB2, or the existence of the TERT C228T mutation indicated disease progression. Stable cfDNA levels, normal ERBB2 copy number, and the absence of TERT C228T mutations indicate a stable cancer status. Collectively, our results show that the combination of cfDNA concentration, TERT mutation, and ERBB2 copy number may be useful for determining the efficacy of drug therapy in patients with metastatic bladder cancer.https://doi.org/10.1038/s41598-023-46977-1
spellingShingle Ryota Ogura
Saya Ito
Takashi Ueda
Yusuke Gabata
Satoshi Sako
Yuta Inoue
Takeshi Yamada
Hirotaka Konishi
Atsuko Fujihara
Osamu Ukimura
Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level
Scientific Reports
title Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level
title_full Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level
title_fullStr Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level
title_full_unstemmed Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level
title_short Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level
title_sort screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell gene level
url https://doi.org/10.1038/s41598-023-46977-1
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