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Publications

Journal Article Epublish

PubMed: 40564403 DOI: 10.3390/bioengineering12060586

Characterization of Parthanatos in Breast Cancer: Implications for Prognosis and PARP Inhibitor Resistance.

Bioengineering (Basel) 12(6)

Authors: Junjie Tang, Qian Liu, Wei Du, Linxi Chen, Feiyang Qi, Ranxin Zhang, Bang H Hoang, David S Geller, Rui Yang, Jichuan Wang, Li Hu

Affiliations

  • Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China. The First Clinical Medical School, Nanjing Medical University, Nanjing 211166, China.
  • Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China.
  • Breast Center, Peking University People's Hospital, Beijing 100044, China.
  • Musculoskleletal Tumor Center, Beijing Key Laboratory for Musculoskeletal Tumors, Peking University People's Hospital, Beijing 100041, China.
  • Department of Orthopedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA.

Abstract

Parthanatos, a novel form of programmed cell death mediated by PARP1 and driven by DNA damage, has not been comprehensively characterized in breast cancer (BC). Given the widespread clinical use of PARP1 inhibitors for treating BRCA-mutant breast cancers, understanding the role of parthanatos is crucial. In this study, we systematically analyzed the role and clinical significance of parthanatos in BC by integrating genomic, transcriptomic, and clinical data. Our analysis revealed significant differential expression of parthanatos-related genes between BC and normal breast tissues, with frequent copy number variations (CNVs) affecting gene expression. At the single-cell level, parthanatos-related genes were primarily expressed in breast cancer cells and macrophages, and genomic instability scores were positively correlated with parthanatos pathway scores. Unsupervised clustering identified two BC subtypes based on parthanatos-related gene expression: C1 (parthanatos-high) and C2 (parthanatos-low). C1 exhibited a poorer prognosis, reduced immune infiltration, and potential resistance to PARP inhibitors compared to C2. This study represents the first comprehensive investigation of parthanatos in BC, offering insights into its role in tumor progression and highlighting its potential link to PARP inhibitor resistance and poor clinical outcomes.

MeSH

Cells, Genes, Poly(Adp-Ribose) Polymerase Inhibitors, Breast Neoplasms, Neoplasms, Parthanatos, Breast, Prognosis, Gene Expression