Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer
Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10539 |
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| author | Chung-Liang Li Sin-Hua Moi Huei-Shan Lin Ming-Feng Hou Fang-Ming Chen Shen-Liang Shih Jung-Yu Kan Chieh-Ni Kao Yi-Chia Wu Li-Chun Kao Ying-Hsuan Chen Yi-Chen Lee Chih-Po Chiang |
| author_facet | Chung-Liang Li Sin-Hua Moi Huei-Shan Lin Ming-Feng Hou Fang-Ming Chen Shen-Liang Shih Jung-Yu Kan Chieh-Ni Kao Yi-Chia Wu Li-Chun Kao Ying-Hsuan Chen Yi-Chen Lee Chih-Po Chiang |
| author_sort | Chung-Liang Li |
| collection | DOAJ |
| description | Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future. |
| first_indexed | 2024-03-09T23:45:42Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:45:42Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-54a29acbbf204502b189a0196e0148222023-11-23T16:43:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181053910.3390/ijms231810539Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast CancerChung-Liang Li0Sin-Hua Moi1Huei-Shan Lin2Ming-Feng Hou3Fang-Ming Chen4Shen-Liang Shih5Jung-Yu Kan6Chieh-Ni Kao7Yi-Chia Wu8Li-Chun Kao9Ying-Hsuan Chen10Yi-Chen Lee11Chih-Po Chiang12Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanCenter of Cancer Program Development, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, TaiwanEndocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future.https://www.mdpi.com/1422-0067/23/18/10539breast cancerendocrine therapy resistancecross-resistanceselective estrogen receptor modulators (SERMs)selective estrogen receptor degraders (SERDs)aromatase inhibitors (AIs) |
| spellingShingle | Chung-Liang Li Sin-Hua Moi Huei-Shan Lin Ming-Feng Hou Fang-Ming Chen Shen-Liang Shih Jung-Yu Kan Chieh-Ni Kao Yi-Chia Wu Li-Chun Kao Ying-Hsuan Chen Yi-Chen Lee Chih-Po Chiang Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer International Journal of Molecular Sciences breast cancer endocrine therapy resistance cross-resistance selective estrogen receptor modulators (SERMs) selective estrogen receptor degraders (SERDs) aromatase inhibitors (AIs) |
| title | Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer |
| title_full | Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer |
| title_fullStr | Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer |
| title_full_unstemmed | Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer |
| title_short | Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer |
| title_sort | comprehensive transcriptomic and proteomic analyses identify a candidate gene set in cross resistance for endocrine therapy in breast cancer |
| topic | breast cancer endocrine therapy resistance cross-resistance selective estrogen receptor modulators (SERMs) selective estrogen receptor degraders (SERDs) aromatase inhibitors (AIs) |
| url | https://www.mdpi.com/1422-0067/23/18/10539 |
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