摘要

Breast cancer (BC) is one of the most common malignant tumours in women, and its prognosis is poor. The prognosis of BC patients can be improved by immunotherapy. However, due to the heterogeneity of BC, the identification of new biomarkers is urgently needed to improve the prognosis of BC patients. Necrotic apoptosis has been shown to play an essential role in many cancers. First, this study proposed a novel clustering algorithm called biorthogonal constrained depth semisupervised nonnegative matrix factorization (DO-DSNMF). The DO-DSNMF algorithm added multilayer nonlinear transformation to the coefficient matrix obtained after decomposition, which was used to mine the nonlinear relationship between samples. In addition, we also added orthogonal constraints on the basis matrix and coefficient matrix to reduce the influence of redundant features and samples on the results. We applied the DO-DSNMF algorithm and analysed the differences in survival and immunity between the subtypes. Then, we used prognosis analysis to construct the prognosis model. Finally, we analysed single cells using single-cell sequencing (scRNA-seq) data from the GSE75688 dataset in the GEO database. We identified two BC subtypes based on the BC transcriptome data in the TCGA database. Immune infiltration analysis showed that the necrotizing apoptosis-related genes of BC were related to various immune cells and immune functions. Necrotizing apoptosis was found to play a role in BC progression and immunity. The role of prognosis-related NRGs in BC was also verified by cell experiments. This study proposed a novel clustering algorithm to analyse BC subtypes and constructed an NRG prognostic model for BC. The prognosis and immune landscape of BC patients were evaluated by this model. The cell experiment supported its role in BC, which provides a potential therapeutic target for the treatment of BC.

  • 单位
    哈尔滨医科大学