Int J Med Sci 2021; 18(12):2521-2531. doi:10.7150/ijms.59177 This issue

Research Paper

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*, Chien-Yu Huang3,6,7,8, Chin-Sheng Hung3,7✉

1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
2. Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
3. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
4. Section of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan, ROC.
5. Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
6. Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
7. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC.
8. Division of Colonrectal Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University.
*Chou, CW and Chang, YJ is contributed equally.

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Citation:
Chou CW, Huang YM, Chang YJ, Huang CY, Hung CS. Identified the novel resistant biomarkers for taxane-based therapy for triple-negative breast cancer. Int J Med Sci 2021; 18(12):2521-2531. doi:10.7150/ijms.59177. Available from https://www.medsci.org/v18p2521.htm

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Abstract

Graphic 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.

Keywords: TNBC, GEO, taxane, bioinformative, basal-like-TNBC.