Open Access

Variant allele frequency changes in TP53 predict pembrolizumab response in patients with metastatic urothelial carcinoma

  • Authors:
    • Kazuki Hamada
    • Yoshiyuki Nagumo
    • Shuya Kandori
    • Kozaburo Tanuma
    • Masanobu Shiga
    • Akio Hoshi
    • Hiromitsu Negoro
    • Takahiro Kojima
    • Bryan J. Mathis
    • Hiroyuki Nishiyama
  • View Affiliations

  • Published online on: July 24, 2023     https://doi.org/10.3892/ol.2023.13975
  • Article Number: 389
  • Copyright: © Hamada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prognoses for patients with metastatic urothelial carcinoma (mUC) have improved with pembrolizumab treatment, an immune checkpoint inhibitor, but clinical benefits are limited to a subset of patients. Therefore, a non‑invasive biomarker to predict pembrolizumab response is required. The present study retrospectively examined genomic alterations in 25 plasma circulating tumor DNA (ctDNA) samples using targeted sequencing of 77 genes from 16 patients with mUC during pembrolizumab treatment. A total of 11 (68.8%) patients demonstrated ≥2 genomic alterations, including TP53 mutations (as defined by ctDNA‑positive status). The proportion of responders to pembrolizumab in the ctDNA‑positive group was higher compared with that in the ctDNA‑negative group (72.7 vs. 20.0%). Furthermore, among all detected genomic alterations, variant allele frequency decreases in TP53 during pembrolizumab treatment were mainly associated with therapeutic response. Collectively, these data suggest that profiling of ctDNA in plasma, particularly TP53, may be useful for predicting and monitoring therapeutic responses to pembrolizumab in patients with mUC.
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September-2023
Volume 26 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Hamada K, Nagumo Y, Kandori S, Tanuma K, Shiga M, Hoshi A, Negoro H, Kojima T, Mathis BJ, Nishiyama H, Nishiyama H, et al: Variant allele frequency changes in TP53 predict pembrolizumab response in patients with metastatic urothelial carcinoma. Oncol Lett 26: 389, 2023
APA
Hamada, K., Nagumo, Y., Kandori, S., Tanuma, K., Shiga, M., Hoshi, A. ... Nishiyama, H. (2023). Variant allele frequency changes in TP53 predict pembrolizumab response in patients with metastatic urothelial carcinoma. Oncology Letters, 26, 389. https://doi.org/10.3892/ol.2023.13975
MLA
Hamada, K., Nagumo, Y., Kandori, S., Tanuma, K., Shiga, M., Hoshi, A., Negoro, H., Kojima, T., Mathis, B. J., Nishiyama, H."Variant allele frequency changes in TP53 predict pembrolizumab response in patients with metastatic urothelial carcinoma". Oncology Letters 26.3 (2023): 389.
Chicago
Hamada, K., Nagumo, Y., Kandori, S., Tanuma, K., Shiga, M., Hoshi, A., Negoro, H., Kojima, T., Mathis, B. J., Nishiyama, H."Variant allele frequency changes in TP53 predict pembrolizumab response in patients with metastatic urothelial carcinoma". Oncology Letters 26, no. 3 (2023): 389. https://doi.org/10.3892/ol.2023.13975