Deciphering Proteoform Landscape of Mammary Carcinoma by Top-Down Proteomics

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Defining the proteoform landscape of breast cancer can provide unique insights into signaling pathways driving disease progression. While bottom-up proteomics has been utilized to profile cancer, it lacks ability capture intact proteoforms that may underpin disease. Top-down is ideally suited characterize proteoforms; however, most top-down studies have limited low molecular weight (MW) proteins (<50 kDa). Herein, we employed a two-dimensional (2D) liquid chromatography combining size exclusion (SEC) with reverse phase (RPC) followed by high-resolution mass spectrometry (MS) expand coverage for high MW proteoforms. Using this 2D-SEC-RPC-MS approach, observed 5-fold increase in detection (>50 kDa) compared conventional 1D-RPC-MS. SEC separation significantly enhanced (>104 kDa), including intermediate filament proteins, vimentin and keratins. Based on accurate measurements MS/MS data, identified 775 from both TFA HEPES extracts detected PTMs, such as acetylation, glutathionylation, myristoylation. Pathway analysis uncovered many involved processes dysregulated Overall, our findings illustrate power defining carcinoma.

Language: Английский

Proteomics in Diagnostic Evaluation and Treatment of Breast Cancer: A Scoping Review

Journal of Personalized Medicine, Journal Year: 2025, Volume and Issue: 15(5), P. 177 - 177

Published: April 27, 2025

Objectives: The aim of this scoping review was to delineate the current role and possible applications proteomics in personalized breast cancer diagnostic evaluation treatment. Methods: A comprehensive search PubMed/MEDLINE Scopus/EMBASE conducted, according PRISMA–ScR guidelines. Inclusion criteria: proteomic studies specimens from patients, clinically relevant clinical studies. Exclusion silico, vitro animal models, articles, case reports, series, comments, editorials, articles language other than English. study protocol registered Open Science Framework. Results: In total, 1093 records were identified, 170 papers retrieved 140 selected for data extraction. Data analysis synthesis evidence showed that most analyses conducted tumor (n = 77), followed by blood samples 48), less frequently biologic material taken patients 19). commonly used methods liquid chromatography–tandem mass spectrometry (LC–MS/MS), Matrix-assisted laser desorption/ionization-time flight (MALDI–TOF), Surface-Enhanced Laser Desorption/Ionization Time-of-Flight (SELDI–TOF) Reverse Phase Protein Arrays (RPPA). Conclusions: present provides a thorough map published literature reporting results yielded various biological different subgroups patients. This shows that, although are not currently everyday practice guide decision-making, nevertheless numerous proteins identified could be as biomarkers treatment

Language: Английский