Quantitative Glycoproteomics In The Study Of Triple-Negative Breast Cancer With Different Prognosis

Triple-negative breast cancer(TNBC)is a pathological subtype of breast cancer,which is insensitive to common hormone therapy and targeted therapy and has a poor prognosis.At present,there is still a lack of reliable biomarkers that can distinguish triple-negative breast cancer and its different prognosis.It was shown that the occurrence and development of tumors are closely related to the glycosylation modification of proteins,and there are abnormal glycosylation modifications in cancer tissues of patients.However,up to now,there are few studies on abnormal glycosylation modification of triple-negative breast cancer.Therefore,we combined proteomics with high-throughput and site-specific glycoproteomics to quantitatively detect the level of protein and glycosylation modification in patients with triple-negative breast cancer.The study of the molecular characteristics and functional pathways of differential proteins and glycosylated proteins in the different prognosis of cancer provided more abundant references for diagnosis and treatment of triple-negative breast cancer patients.The main research results are summarized as follows:(1)In this study,cancer tissues and paired non-cancerous adjacent tissues(NATs)of 9patients with good prognosis and 9 patients with poor prognosis were collected.The hydrolyzed peptides were quantitatively analyzed by tandem mass tag(TMT)labeling,and glycopeptides were enriched by hydrophilic column.(2)Through the functional and KEGG pathway enrichment analysis of differential proteins,it was found that the highly expressed proteins in cancer tissues were mainly involved in biological pathways such as cell adhesion,cell migration,and change of extracellular matrix,which promoted the invasion of tumor cells.Through the analysis of different prognosis of cancer,it was found that the expression of histone H1.2 was the highest in cancer tissues with poor prognosis,which promoted the growth and development of cancer cells.(3)Through the functional and KEGG pathway enrichment analysis of differential glycosylation modification in cancer tissues and non-cancerous adjacent tissues showed that glycosylation of glycoprotein hemoglobin and antithrombin III may promote cancer metastasis and invasion.Based on the analysis of glycosylation modification with different prognosis,it was found that 25 glycoproteins with high expression in patients with good prognosis were associated with extracellular matrix-receptor pathway and human papillomavirus infection by KEGG pathway analysis.These pathways are closely related to cancer cell differentiation and metastasis,among which PI3K/AKT pathway is one of the common maladjusted signal pathways in triple-negative breast cancer.(4)According to the differential protein glycosylation modification of triple-negative breast cancer tissues,glycoprotein CO6A6,DCN,and COCA1 are predictive biomarkers for patients with good prognosis,poor prognosis,and triple-negative breast cancer patients,respectively.It is worth noting that there are differences in the glycosylation on the same glycosites of glycoproteins in cancer tissues with different prognosis.This study explained the molecular characteristics and functions of triple-negative breast cancer and its different prognosis from the differential glycosylation modification level and provided effective therapeutic strategy support for the search for biomarkers of triple-negative breast cancer.