4.7 Article

Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer

期刊

出版社

MDPI
DOI: 10.3390/ijms231810539

关键词

breast cancer; endocrine therapy resistance; cross-resistance; selective estrogen receptor modulators (SERMs); selective estrogen receptor degraders (SERDs); aromatase inhibitors (AIs); The Cancer Genome Atlas (TCGA)

资金

  1. [MOST 109-2314-B-037-038]
  2. [110-2314-B-037-109]
  3. [KMUH110-0R40]
  4. [EDCHT111002]
  5. [QCR18001]

向作者/读者索取更多资源

This study identifies candidate gene sets that play critical roles in the resistance of endocrine therapy for hormone-receptor-positive breast cancer. These gene sets can differentiate different treatment response groups and are significantly correlated with survival outcomes. This has important clinical implications for the diagnosis, mechanism, and therapeutic strategy in the future.
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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据