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Updated: Nov 2, 2025
Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
Published on: February 20, 2017
Identified the novel resistant biomarkers for taxane-based therapy for triple-negative breast cancer
Ching-Wen Chou1,2, Yu-Min Huang3,4, Yu-Jia Chang1,5,6
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
Abstract:
Developing treatment strategies for triple-negative breast cancer (TNBC) has become an important clinical challenge. Currently, taxane-based chemotherapy is one of the standard treatments for TNBC. However, determining the key factor of taxane-resistance is urgently in need for clinical treatment for breast cancer. We used GEO data to generate paclitaxel resistance in two basal-like TNBC cell lines (SUM149 and MDA-MB-468). Seventy-one common upregulated differentially expressed genes (DEGs) and 11 downregulated DEGs were found to be related to paclitaxel resistance. By constructing protein-protein interactions, 28 hub proteins with a degree cutoff criterion of ≥1 were found. Nine hub genes (COL4A6, COL4A5, IL6, PDGFA, LPAR1, FYB, IL20, IL18R1 and INHBA) are involved in important signaling pathways. We found that upregulated PDGFA and downregulated COL4A6 were significantly associated with an insensitive response to neoadjuvant paclitaxel-based therapy. A Kaplan-Meier plot was created to check the prognostic values of 11 hub DEGs in terms of recurrence-free survival. High expressions of PDGFA and LAMB3 were correlated with poor recurrence-free survival, while low levels of FYB, IL18R1, and RASGRP1 indicated poorer relapse-free survival. Our results suggest that PDGFA, COL4A6, LPAR1, FYB, COL4A5, and RASGRP1 might be candidate target genes for taxane-based therapy in basal-like TNBC.
Insights
Identifying key genes for paclitaxel resistance in triple-negative breast cancer (TNBC) is crucial. This study found specific genes, like PDGFA and COL4A6, linked to treatment response and patient survival in basal-like TNBC.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) presents significant clinical challenges, with taxane-based chemotherapy as a standard treatment.
- Understanding the mechanisms of taxane resistance is critical for improving clinical outcomes in breast cancer patients.
- Basal-like TNBC subtypes require specific therapeutic strategies to overcome treatment resistance.
Purpose of the Study:
- To identify key genes associated with paclitaxel resistance in basal-like TNBC.
- To explore the prognostic value of identified genes in relation to patient survival.
- To propose candidate target genes for enhancing taxane-based therapy efficacy in TNBC.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) data to model paclitaxel resistance in TNBC cell lines (SUM149, MDA-MB-468).
- Analyzed differentially expressed genes (DEGs) and constructed protein-protein interaction networks to identify hub genes.
- Correlated gene expression with clinical response to neoadjuvant paclitaxel therapy and assessed prognostic value using Kaplan-Meier analysis.
Main Results:
- Identified 71 common upregulated and 11 downregulated DEGs related to paclitaxel resistance.
- Discovered nine hub genes involved in critical signaling pathways, with PDGFA (upregulated) and COL4A6 (downregulated) linked to therapy insensitivity.
- High PDGFA and LAMB3 expression correlated with poor recurrence-free survival; low FYB, IL18R1, and RASGRP1 indicated poorer relapse-free survival.
Conclusions:
- PDGFA and COL4A6 are significantly associated with response to paclitaxel-based neoadjuvant therapy in basal-like TNBC.
- Several identified hub genes, including PDGFA, LAMB3, FYB, IL18R1, and RASGRP1, demonstrate prognostic value for patient survival.
- PDGFA, COL4A6, LPAR1, FYB, COL4A5, and RASGRP1 are proposed as potential therapeutic targets for taxane-based treatments in basal-like TNBC.
