Construction and characterization of a cuproptosis- and immune checkpoint-based LncRNAs signature for breast cancer risk stratification.

Background: Cuproptosis is the most recently identified form of cell death, and copper homeostasis is an important cancer therapeutic target. However, the therapeutic benefits of cuproptosis-targeted treatment in BRCA remain undetermined. This study utilized LncRNAs linked to cuproptosis genes and immune checkpoint genes to generate a BRCA predictive signature.

Methods: We screened a population of LncRNAs that correlated with both cuproptosis genes and immune checkpoint genes and used ten of these LncRNAs to construct a prognosis-predictive signature. We then validated and proved the efficacy of the signature in predicting the prognosis of BRCA patients. We also unraveled the relationship between the signature and the immunological milieu, immune function, and susceptibility to chemotherapy.

Results: The signature derived from the ten cuproptosis- and immune-related prognostic LncRNAs (CuImP-LncRNAs) can be implied to categorize patients into two groups, including the high- and low-risk groups. The value of the signature was validated, and the risk score was verified as an independent prognostic indicator. The TIME and TMB distribution patterns and chemosensitivity were depicted in the high- and low-risk groups, respectively. Patients of the high-risk group with a suppressive immunological intratumor context were more sensitive to a broad range of antitumor agents. In contrast, low-risk individuals with active immune function responded more favorably to immunotherapy.

Conclusion: Our findings provided a novel and effective model for predicting BRCA prognosis and the propensity to different treatment modalities, thus contributing to the optimization of personalized BRCA therapy in the future.