Gbp5 serves as a potential marker to predict a favorable response in triple-negative breast cancer patients receiving a taxane-based chemotherapy

Shun Wen Cheng, Po Chih Chen, Tzong Rong Ger, Hui Wen Chiu, Yuan Feng Lin

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Pre-operative (neoadjuvant) or post-operative (adjuvant) taxane-based chemotherapy is still commonly used to treat patients with triple-negative breast cancer (TNBC). However, there are still no effective biomarkers used to predict the responsiveness and efficacy of taxane-based chemotherapy in TNBC patients. Here we find that guanylate-binding protein 5 (GBP5), compared to other GBPs, exhibits the strongest prognostic significance in predicting TNBC recurrence and progression. Whereas GBP5 upregulation showed no prognostic significance in non-TNBC patients, a higher GBP5 level predicted a favorable recurrence and progression-free condition in the TNBC cohort. Moreover, we found that GBP5 expression negatively correlated with the 50% inhibitory concentration (IC50) of paclitaxel in a panel of TNBC cell lines. The gene knockdown of GBP5 increased the IC50 of paclitaxel in the tested TNBC cells. In TNBC patients receiving neoadjuvant or adjuvant chemotherapy, a higher GBP5 level strongly predicted a good responsiveness. Computational simulation by the Gene Set Enrichment Analysis program and cell-based assays demonstrated that GBP5 probably enhances the cytotoxic effectiveness of paclitaxel via activating the Akt/mTOR signaling axis and suppressing autophagy formation in TNBC cells. These findings suggest that GBP5 could be a good biomarker to predict a favorable outcome in TNBC patients who decide to receive a taxane-based neoadjuvant or adjuvant therapy.

Original languageEnglish
Article number197
JournalJournal of Personalized Medicine
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2021

Keywords

  • Akt/mTOR
  • Autophagy
  • Chemotherapy
  • GBP5
  • Taxane
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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