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GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients
BACKGROUND: Investigations of the 21-gene Oncotype DX assay in neoadjuvant settings for breast cancer patients are currently underdeveloped. It is still unclear whether any individual gene of the 16 cancer-related genes can be used to predict response to taxane-based neoadjuvant chemotherapy. METHOD...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797896/ https://www.ncbi.nlm.nih.gov/pubmed/35116798 http://dx.doi.org/10.21037/tcr.2019.04.03 |
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author | Zhang, Guochun Qian, Xueke Ren, Chongyang Wen, Lingzhu Lyu, Haitong Liao, Ning |
author_facet | Zhang, Guochun Qian, Xueke Ren, Chongyang Wen, Lingzhu Lyu, Haitong Liao, Ning |
author_sort | Zhang, Guochun |
collection | PubMed |
description | BACKGROUND: Investigations of the 21-gene Oncotype DX assay in neoadjuvant settings for breast cancer patients are currently underdeveloped. It is still unclear whether any individual gene of the 16 cancer-related genes can be used to predict response to taxane-based neoadjuvant chemotherapy. METHODS: Here, we performed TaqMan RT-PCR reactions to profile the expression patterns of these genes in 66 Chinese ER-positive breast cancer patients’ tumor tissues who underwent taxane-based neoadjuvant chemotherapies. Only GSTM1 has distinct non-expression/expression polymorphism, and we observed an almost 2.5-fold increment in the possibility of achieving pathological complete response (pCR) was defined as no histological evidence of residual invasive cancer both in the breast and in the axilla. in GSTM1 non-expression patients. We then analyzed the expression levels of 4 main GST isozymes (GSTA1, GSTT1, GSTP1 and GSTT1) and docetaxel cytotoxicity in various breast cancer cell lines (MCF7, MDA-MB-231, BT474, and SKBR3). Furthermore, we knocked down 4 GST isozymes with siRNA against each isoform in resistant MDA-MB-231. We then observed the changes of docetaxel sensitivity though WST-1 assay, in addition to apoptosis by Hoechst stain and TUNEL assay. RESULTS: Docetaxel IC50 values ranging from 33.0 nM (MDA-MB-231) to 7.20 µM (resistant MDA-MB-231) revealed a close correlation with the expression levels of 4 main GST isozymes. Significantly, depletion of GSTM1 and GSTA1 but not GSTP1 nor GSTT1, suppressed cell viability by 174% and 155% respectively, and was able to induce obvious apoptosis in resistant MDA-MB-132. CONCLUSIONS: Taken together, our results suggest that GSTM1 polymorphism could be useful in the prediction of taxane-based neoadjuvant chemotherapy in ER-positive Chinese breast cancer patients, and that GSTM1 and GSTA1 expression are linked to docetaxel resistance. |
format | Online Article Text |
id | pubmed-8797896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-87978962022-02-02 GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients Zhang, Guochun Qian, Xueke Ren, Chongyang Wen, Lingzhu Lyu, Haitong Liao, Ning Transl Cancer Res Original Article BACKGROUND: Investigations of the 21-gene Oncotype DX assay in neoadjuvant settings for breast cancer patients are currently underdeveloped. It is still unclear whether any individual gene of the 16 cancer-related genes can be used to predict response to taxane-based neoadjuvant chemotherapy. METHODS: Here, we performed TaqMan RT-PCR reactions to profile the expression patterns of these genes in 66 Chinese ER-positive breast cancer patients’ tumor tissues who underwent taxane-based neoadjuvant chemotherapies. Only GSTM1 has distinct non-expression/expression polymorphism, and we observed an almost 2.5-fold increment in the possibility of achieving pathological complete response (pCR) was defined as no histological evidence of residual invasive cancer both in the breast and in the axilla. in GSTM1 non-expression patients. We then analyzed the expression levels of 4 main GST isozymes (GSTA1, GSTT1, GSTP1 and GSTT1) and docetaxel cytotoxicity in various breast cancer cell lines (MCF7, MDA-MB-231, BT474, and SKBR3). Furthermore, we knocked down 4 GST isozymes with siRNA against each isoform in resistant MDA-MB-231. We then observed the changes of docetaxel sensitivity though WST-1 assay, in addition to apoptosis by Hoechst stain and TUNEL assay. RESULTS: Docetaxel IC50 values ranging from 33.0 nM (MDA-MB-231) to 7.20 µM (resistant MDA-MB-231) revealed a close correlation with the expression levels of 4 main GST isozymes. Significantly, depletion of GSTM1 and GSTA1 but not GSTP1 nor GSTT1, suppressed cell viability by 174% and 155% respectively, and was able to induce obvious apoptosis in resistant MDA-MB-132. CONCLUSIONS: Taken together, our results suggest that GSTM1 polymorphism could be useful in the prediction of taxane-based neoadjuvant chemotherapy in ER-positive Chinese breast cancer patients, and that GSTM1 and GSTA1 expression are linked to docetaxel resistance. AME Publishing Company 2019-04 /pmc/articles/PMC8797896/ /pubmed/35116798 http://dx.doi.org/10.21037/tcr.2019.04.03 Text en 2019 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Original Article Zhang, Guochun Qian, Xueke Ren, Chongyang Wen, Lingzhu Lyu, Haitong Liao, Ning GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients |
title | GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients |
title_full | GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients |
title_fullStr | GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients |
title_full_unstemmed | GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients |
title_short | GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients |
title_sort | gstm1 polymorphism in oncotype dx assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive chinese breast cancer patients |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797896/ https://www.ncbi.nlm.nih.gov/pubmed/35116798 http://dx.doi.org/10.21037/tcr.2019.04.03 |
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