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
Funding Information:

• The National Natural Science Foundation of China (No. 82103695, No. 82303865, No. 82173115)
• Shanghai Rising-Star Program (No. 22QC1400200)
• Shanghai Municipal Health Commission Health Industry Clinical Research Special Project (China) (No. 202340085)
• The Nurturing Fund of Renji Hospital (Shanghai, China) (No. PYIII20-09)

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