Chromatin Remodeling Enzyme Cluster Predicts Prognosis and Clinical Benefit of Therapeutic Strategy in Breast Cancer

Int J Mol Sci. 2023 Mar 15;24(6):5583. doi: 10.3390/ijms24065583.

Abstract

The treatment provided for breast cancer depends on the expression of hormone receptors, human epidermal growth factor receptor-2 (HER2), and cancer staging. Surgical intervention, along with chemotherapy or radiation therapy, is the mainstay of treatment. Currently, precision medicine has led to personalized treatment using reliable biomarkers for the heterogeneity of breast cancer. Recent studies have shown that epigenetic modifications contribute to tumorigenesis through alterations in the expression of tumor suppressor genes. Our aim was to investigate the role of epigenetic modifications in genes involved in breast cancer. A total of 486 patients from The Cancer Genome Atlas Pan-cancer BRCA project were enrolled in our study. Hierarchical agglomerative clustering analysis further divided the 31 candidate genes into 2 clusters according to the optimal number. Kaplan-Meier plots showed worse progression-free survival (PFS) in the high-risk group of gene cluster 1 (GC1). In addition, the high-risk group showed worse PFS in GC1 with lymph node invasion, which also presented a trend of better PFS when chemotherapy was combined with radiotherapy than when chemotherapy was administered alone. In conclusion, we developed a novel panel using hierarchical clustering that high-risk groups of GC1 may be promising predictive biomarkers in the clinical treatment of patients with breast cancer.

Keywords: chemotherapy; chromatin remodeling enzyme; epigenetic modification; hierarchical clustering; radiotherapy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / therapy
  • Chemotherapy, Adjuvant
  • Chromatin
  • Chromatin Assembly and Disassembly
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Receptor, ErbB-2 / metabolism

Substances

  • Chromatin
  • Receptor, ErbB-2
  • Biomarkers, Tumor

Grants and funding

This research was funded by the following grants: (1) KMHK-DK(C)111003, KMUH-DK-109001, KMUH110-0T04, and KMUH111-1R34 from the Kaohsiung Medical University Hospital; (2) 111-2320-B-037-030, 111-2628-B-037-008, 110-2320-B-037-006, 111-2321-B-037-002, 111-2320-B-037-030, 110-2321-B-037-002, 109-2314-B-037-019, 109-2314-B-037-132-, and 109-2314-B-037-036-MY3 from the National Science and Technology Council, Taiwan. The APC was funded by 109-2314-B-037-036-MY3.