image: Flow chart of this study.
Credit: Huiling Wang, Huijuan Dai, Yaohui Wang, Qiong Wu, Mingxi Zhu, Wenjin Yin, Jinsong Lu
This new research, published in the Genes & Diseases journal by a team from Renji Hospital, School of Medicine, Shanghai Jiao Tong University, investigated a novel CIN-related gene signature to comprehensively predict breast cancer survival outcomes and immunotherapy responses.
Utilizing transcriptome sequencing data from large clinical cohorts, the researchers performed unsupervised consensus clustering based on the established CIN25 gene signature. Through rigorous statistical models, including LASSO and multivariate Cox regression analyses, they successfully constructed a streamlined 13-gene prognostic model termed the "CIN score".
Clinical cohort analyses revealed that patients with a high CIN score exhibit significantly poorer overall survival and unfavorable clinicopathological features. Furthermore, comprehensive multi-omics and single-cell RNA sequencing (scRNA-seq) analyses demonstrated that the immune landscape drastically differs based on this signature.
The low-CIN score group is characterized by a highly active immune microenvironment, showing enriched infiltration of critical anti-tumor immune cells, including CD8+ T cells and activated dendritic cells, as well as significantly elevated expression of key immune checkpoints like PD-1 and CTLA-4. Conversely, high-CIN score tumors exhibited strong immunosuppressive traits and heightened interactions with stromal cells via pathways like VEGF, promoting tumor metastasis.
Remarkably, extensive drug sensitivity analyses confirmed that a high CIN score accurately predicts profound cellular resistance to multiple commonly used chemotherapeutic, endocrine, and targeted agents, such as paclitaxel, cisplatin, and tamoxifen.
While these collective data robustly highlight the vital role of the CIN score in evaluating tumor aggressiveness and the surrounding immune landscape, additional prospective multicenter clinical trials are needed to fully validate its routine use in clinical settings.
In conclusion, this study establishes the CIN score as a clinically relevant biomarker that integrates genomic instability with immune profiling. By enabling improved risk stratification and guiding therapeutic decision-making, the CIN score offers a promising tool for advancing precision medicine in breast cancer.
Reference
Title of Original Paper: Leveraging a chromosomal instability-based signature to predict the prognosis and immune landscape of breast cancer
Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.
DOI: https://doi.org/10.1016/j.gendis.2025.101924
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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