| Breast cancer is the tumor with the highest incidence among women through the world.Defined as estrogen receptor-negative,progesterone receptor-negative,and human epidermal growth factor receptor 2-negative,triple-negative breast cancer(TNBC)is the most difficult breast cancer to cure in clinical practice.Even with the same pathological type,the same clinical stage and experienced the same treatment process,the prognosis of patients with TNBC is still quite different,indicating that there is a high inter-tumor heterogeneity within this disease.With a multi-omics integrated method,this study first divided TNBC samples of the Chinese population into five different subtypes with integration of transcriptome,whole exome sequencing and CNV data,and then comprehensively analyzed the clinical characteristics and molecular mutation spectrum of each subtype.Next,we analyzed the potential drugs of TNBC samples by means of pathway enrichment of somatic mutations,subtype-specific highly expressed genes and genetic interaction.Since human cancer is a dynamic disease that will gradually develop over a long period through the accumulation of a series of genetic mutations,this study adopted Monocle’s pseudo-time series analysis to explore the developmental differences between different TNBC samples.As a result,a tree model of TNBC progression which showed the correlation between the state of different samples and their intrinsic molecular characteristics has been built.Finally,we explored the radiotherapy and chemotherapy information of 1,218 TCGA(The Cancer Genome Atlas)breast cancer samples to explore the sensitivity of radiotherapy /chemotherapy under different breast cancer subtypes frameworks and provided references and ideas for the treatment of various TNBC subtypes. |
