Open Access

Discovering novel mechanisms of taxane resistance in human breast cancer by whole‑exome sequencing

  • Authors:
    • Yumi Wanifuchi-Endo
    • Naoto Kondo
    • Yu Dong
    • Takashi Fujita
    • Tomoko Asano
    • Tomoka Hisada
    • Yasuaki Uemoto
    • Sayaka Nishikawa
    • Yusuke Katagiri
    • Akiko Kato
    • Mitsuo Terada
    • Hiroshi Sugiura
    • Katsuhiro Okuda
    • Hiroyuki Kato
    • Satoru Takahashi
    • Tatsuya Toyama
  • View Affiliations

  • Published online on: December 22, 2021     https://doi.org/10.3892/ol.2021.13178
  • Article Number: 60
  • Copyright: © Wanifuchi-Endo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Taxanes are important drugs used in the treatment of breast cancer; however, some cancer types are taxane‑resistant. The aim of the present study was to investigate the underlying mechanisms of taxane resistance using whole‑exome sequencing (WES). Six patients with breast cancer whose tumors responded well to anthracycline treatment but grew rapidly during neoadjuvant taxane‑based chemotherapy, were included in the present study. WES of samples from these patients was carried out to identify somatic mutations of candidate genes thought to affect taxane resistance, and the candidate proteins were structurally modeled. The mRNA and protein expression levels of these candidate genes in other breast cancers treated with taxanes were also examined. Nine variants common to all six patients were identified and two of these [R552P in V‑type proton ATPase catalytic subunit A (ATP6V1A) and T114P in apolipoprotein B MRNA editing enzyme catalytic subunit 3F (APOBEC3F)] were selected. The results also showed that, protein‑structure visualization suggested that these mutations may cause structural changes. The Kaplan‑Meier analyses revealed that higher APT6V1A and APOBEC3F expression levels were significantly associated with poorer disease‑free survival (DFS) and overall survival. Moreover, multivariate analysis identified high ATP6V1A mRNA expression as an independent risk factor for poor DFS. Two specific mutations that might affect taxane resistance were identified. Thus, these results suggest that breast cancer patients receiving taxanes who have high ATP6V1A or APOBEC3F expression levels may have shorter survival.
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February-2022
Volume 23 Issue 2

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

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Copy and paste a formatted citation
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Spandidos Publications style
Wanifuchi-Endo Y, Kondo N, Dong Y, Fujita T, Asano T, Hisada T, Uemoto Y, Nishikawa S, Katagiri Y, Kato A, Kato A, et al: Discovering novel mechanisms of taxane resistance in human breast cancer by whole‑exome sequencing. Oncol Lett 23: 60, 2022
APA
Wanifuchi-Endo, Y., Kondo, N., Dong, Y., Fujita, T., Asano, T., Hisada, T. ... Toyama, T. (2022). Discovering novel mechanisms of taxane resistance in human breast cancer by whole‑exome sequencing. Oncology Letters, 23, 60. https://doi.org/10.3892/ol.2021.13178
MLA
Wanifuchi-Endo, Y., Kondo, N., Dong, Y., Fujita, T., Asano, T., Hisada, T., Uemoto, Y., Nishikawa, S., Katagiri, Y., Kato, A., Terada, M., Sugiura, H., Okuda, K., Kato, H., Takahashi, S., Toyama, T."Discovering novel mechanisms of taxane resistance in human breast cancer by whole‑exome sequencing". Oncology Letters 23.2 (2022): 60.
Chicago
Wanifuchi-Endo, Y., Kondo, N., Dong, Y., Fujita, T., Asano, T., Hisada, T., Uemoto, Y., Nishikawa, S., Katagiri, Y., Kato, A., Terada, M., Sugiura, H., Okuda, K., Kato, H., Takahashi, S., Toyama, T."Discovering novel mechanisms of taxane resistance in human breast cancer by whole‑exome sequencing". Oncology Letters 23, no. 2 (2022): 60. https://doi.org/10.3892/ol.2021.13178