TY - JOUR
T1 - Proteomic analysis of diabetic retinopathy identifies potential plasma-protein biomarkers for diagnosis and prognosis
AU - Honoré, Bent
AU - Hajari, Javad Nouri
AU - Pedersen, Tobias Torp
AU - Ilginis, Tomas
AU - Al-Abaiji, Hajer Ahmad
AU - Lønkvist, Claes Sepstrup
AU - Saunte, Jon Peiter
AU - Olsen, Dorte Aalund
AU - Brandslund, Ivan
AU - Vorum, Henrik
AU - Slidsborg, Carina
N1 - © 2024 Walter de Gruyter GmbH, Berlin/Boston.
PY - 2024/5
Y1 - 2024/5
N2 - OBJECTIVES: To identify molecular pathways and prognostic- and diagnostic plasma-protein biomarkers for diabetic retinopathy at various stages.METHODS: This exploratory, cross-sectional proteomics study involved plasma from 68 adults, including 15 healthy controls and 53 diabetes patients for various stages of diabetic retinopathy: non-diabetic retinopathy, non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and diabetic macular edema. Plasma was incubated with peptide library beads and eluted proteins were tryptic digested, analyzed by liquid chromatography-tandem mass-spectrometry followed by bioinformatics.RESULTS: In the 68 samples, 248 of the 731 identified plasma-proteins were present in all samples. Analysis of variance showed differential expression of 58 proteins across the five disease subgroups. Protein-Protein Interaction network (STRING) showed enrichment of various pathways during the diabetic stages. In addition, stage-specific driver proteins were detected for early and advanced diabetic retinopathy. Hierarchical clustering showed distinct protein profiles according to disease severity and disease type.CONCLUSIONS: Molecular pathways in the cholesterol metabolism, complement system, and coagulation cascade were enriched in patients at various stages of diabetic retinopathy. The peroxisome proliferator-activated receptor signaling pathway and systemic lupus erythematosus pathways were enriched in early diabetic retinopathy. Stage-specific proteins for early - and advanced diabetic retinopathy as determined herein could be 'key' players in driving disease development and potential 'target' proteins for future therapies. For type 1 and 2 diabetes mellitus, the proteomic profiles were especially distinct during the early disease stage. Validation studies should aim to clarify the role of the detected molecular pathways, potential biomarkers, and potential 'target' proteins for future therapies in diabetic retinopathy.
AB - OBJECTIVES: To identify molecular pathways and prognostic- and diagnostic plasma-protein biomarkers for diabetic retinopathy at various stages.METHODS: This exploratory, cross-sectional proteomics study involved plasma from 68 adults, including 15 healthy controls and 53 diabetes patients for various stages of diabetic retinopathy: non-diabetic retinopathy, non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and diabetic macular edema. Plasma was incubated with peptide library beads and eluted proteins were tryptic digested, analyzed by liquid chromatography-tandem mass-spectrometry followed by bioinformatics.RESULTS: In the 68 samples, 248 of the 731 identified plasma-proteins were present in all samples. Analysis of variance showed differential expression of 58 proteins across the five disease subgroups. Protein-Protein Interaction network (STRING) showed enrichment of various pathways during the diabetic stages. In addition, stage-specific driver proteins were detected for early and advanced diabetic retinopathy. Hierarchical clustering showed distinct protein profiles according to disease severity and disease type.CONCLUSIONS: Molecular pathways in the cholesterol metabolism, complement system, and coagulation cascade were enriched in patients at various stages of diabetic retinopathy. The peroxisome proliferator-activated receptor signaling pathway and systemic lupus erythematosus pathways were enriched in early diabetic retinopathy. Stage-specific proteins for early - and advanced diabetic retinopathy as determined herein could be 'key' players in driving disease development and potential 'target' proteins for future therapies. For type 1 and 2 diabetes mellitus, the proteomic profiles were especially distinct during the early disease stage. Validation studies should aim to clarify the role of the detected molecular pathways, potential biomarkers, and potential 'target' proteins for future therapies in diabetic retinopathy.
KW - Adult
KW - Aged
KW - Biomarkers/blood
KW - Blood Proteins/analysis
KW - Cross-Sectional Studies
KW - Diabetic Retinopathy/diagnosis
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Protein Interaction Maps
KW - Proteomics/methods
KW - Tandem Mass Spectrometry
KW - proteomics
KW - disease mechanisms
KW - plasma-protein biomarkers
KW - diabetic retinopathy
KW - liquid chromatography-tandem mass spectrometry
UR - http://www.scopus.com/inward/record.url?scp=85184796948&partnerID=8YFLogxK
U2 - 10.1515/cclm-2023-1128
DO - 10.1515/cclm-2023-1128
M3 - Journal article
C2 - 38332693
SN - 1434-6621
VL - 62
SP - 1177
EP - 1197
JO - Clinical Chemistry and Laboratory Medicine
JF - Clinical Chemistry and Laboratory Medicine
IS - 6
ER -