| BackgroundBreast cancer is the most common malignant tumor in women worldwide,and the morbidity is increasing each year.Its pathogenesis is unknown and many factors can lead to the diseases.Studies suggested that genetic factors play an important role in the development of breast cancer.In recent years,researches on genetic studies of breast cancer including genome-wide association study,genome research,transcriptome research and long non-coding RNA aim to find the susceptibility and pathogenic factors associated with breast cancer from various perspectives and to follow up studies on the mechanism of the disease.With the promotion of numerous studies,many tumor markers have been found and started to be used in clinical treatment.With high heterogeneity and complexity of cancer,the current genetic research not entirely reflect the complex pathogenesis and biological changes of tumors.Therefore,there is still a long way to go for the study of the disease and need to study in different points of view and directions.As a vehicle for gene expression and product,proteins have importantly biological function in human body,as well as in development,metastasis of tumor and clinical test,prognosis and treatment on late stages.So,proteomics has an irreplaceable role in development,metastasis of diseases and promoting of precise health.With recent advances in markable biotechnology,mass spectrometry(MS)serves as the mainstream current and future proteomic analysis method,allowing the possibility to study the characteristics and mechanisms of human cancers in a high-throughput manner with high resolution.In this study,we compared cancer to adjacent normal tissue of the same breast cancer patient using quantitative proteome and lysine succinylome analyses to explore differentially expressed proteins in breast cancer,which provides clues to the pathogenesis of breast cancer.ObjectiveIn this study,we carried out quantitative proteome and lysine succinylome analyses in breast cancer to explore the differentially expressed proteins and to find potential biomarkers in breast cancer,which provide new insights for later research and the development and mechanism of treatment.MethodThree pairs of human breast cancer tissue samples were collected at the No.1 Hospital of Anhui Medical University.Extracting proteins,and then using tandem mass tag(TMT)labeling,high performance liquid chromatography(HPLC)fractionation,anti-succinyllysine antibody-based affinity enrichment and mass spectrometry(MS)-based quantitative proteomics to detect and quantificationally analyze.The markedly changed proteins were analysed with bioinformatics to involve in Gene Ontology(GO)software KEGG database.Results1 Proteomics: In total,141 differentially expressed proteins were obtained in each group including 48 up-regulated proteins and 93 down-regulated proteins with the threshold >1.5 fold change(P-value <0.05.).These differentially expressed proteins were significantly enriched in intermediate filament especially keratin.2 Lysine Succinylome: Altogether,158 lysine succinylation sites in 120 proteins were identified,of which 102 up-regulated lysine succinylation sites on 88 proteins and 93 down-regulated sites on 68 proteins showed altered succinylation levels with the threshold >2.0 fold change(P-value <0.05).And,we found the lysine succinylated proteins were significantly up-regulated in the pentose phosphate pathway(PPP)and the endoplasmic reticulum(ER)protein processing pathway.ConclusionsThis study is the first to detect the proteins lysine succinylated involved regulation and signaling pathway,playing an important role in breast cancer progression.These results screened many proteins associated with breast cancer that could be potential diagnostic biomarkers,laying a foundation for genesis and development of breast cancer. |
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