Recently, a joint research team composed of Massachusetts Institute of Technology, Harvard University, Baylor College of Medicine, New York University and other institutions published an article entitled "Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy" in the Cell Journal, which comprehensively analyzed the breast. The protegenomics of the process of carcinogenesis and its targeted therapy. The results show that proteomics can accurately distinguish breast cancer subtypes, and can more accurately annotate target pathways and biological characteristics of significantly heterogeneous malignant tumors.

The study prospectively collected 122 tumor samples from the early stage of breast cancer treatment, and used proteomics methods to comprehensively process the data, so as to carry out in-depth chemical modification of proteins in cancer cells, phosphorylation and acetylation and other proteins after translation. , Quantitative analysis without offset. Researchers applied the non-negative matrix factorization (NMF) algorithm to the multi-omics data of BRCA classification, and identified four breast cancer subtypes through cluster analysis.

It is known that there are some targeted enzymes called kinases in the subtypes of breast cancer, which have a high degree of phosphorylation. These kinases are candidates for subtype-specific treatments. In order to determine the specific therapeutic target for each NMF subtype, phosphoproteomics research used kinase activation instead. The researchers used outlier enrichment analysis (BlackSheep Python software package) to identify the phosphorylated kinases that were enriched in each NMF subtype.

Subsequently, the researchers used acetyl proteomics analysis to emphasize the acetylation of key nuclear proteins involved in the DNA damage response, revealing the interaction between cytoplasm and mitochondrial acetylation and metabolism. The results of the study indicate that there is a synergistic effect between hypoacetylation and increased protein expression, leading to increased activity of the NMF Basal-I subtype glycolysis pathway; conversely, the hyperacetylation mediated by SIRT3 failure seems to inhibit mitochondrial function.

This study is the first to apply proteomics and acetyl proteomics analysis to a large BRCA cohort study in the context of metabolism, and found that there are significant differences in the expression and acetylation of metabolic enzymes between the luminal and basal enriched subtypes, which may be due to Helps better understand metabolic vulnerability.

The development of protegenomics has brought new diagnostic ideas for breast cancer, which can provide detailed analysis of ERBB2 amplicons for the clinic to determine the subgroup of patients with luminal breast cancer who benefit from immune checkpoint therapy. At the same time, it can also achieve a more accurate prediction of the efficacy of CDK4/6 inhibitors.