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Proteomics-based identification and validation of novel plasma biomarkers phospholipid transfer protein and mannan-binding lectin serine protease-1 in age-related macular degeneration

View Article: PubMed Central - PubMed

ABSTRACT

Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness.

No MeSH data available.


MS/MS profiles of MASP-1 (YFFKDQVLVSCDTGYK) and PLTP (TMLQIGVMPMLNER) peptides; bn and yn denote the fragment ions generated by cleavage of the peptide bond after the nth amino acid containing either the N terminus (b series) or C terminus (y series), respectively.The identified peptide sequence location is shown in bold in the protein sequence.
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f1: MS/MS profiles of MASP-1 (YFFKDQVLVSCDTGYK) and PLTP (TMLQIGVMPMLNER) peptides; bn and yn denote the fragment ions generated by cleavage of the peptide bond after the nth amino acid containing either the N terminus (b series) or C terminus (y series), respectively.The identified peptide sequence location is shown in bold in the protein sequence.

Mentions: Among the potential biomarkers identified in our large-scale quantitative proteomic analysis, the spectral count of PLTP was >11-fold higher in AMD patients than in HCs, leading us to further investigate this protein in the current study. MASP-1 showed a less dramatic spectral count ratio of 1.13 (AMD:HC), but was also examined here owing to its relationship to signalling pathways implicated in AMD development and progression5678. Mass spectral characteristics of the two proteins are shown in Fig. 1 and the Supplementary Datasets. A western blot analysis of 12 patients randomly selected from each group revealed an upregulation of PLTP and MASP-1 expression in AMD patients relative to controls that was dependent on disease severity (Fig. 2).


Proteomics-based identification and validation of novel plasma biomarkers phospholipid transfer protein and mannan-binding lectin serine protease-1 in age-related macular degeneration
MS/MS profiles of MASP-1 (YFFKDQVLVSCDTGYK) and PLTP (TMLQIGVMPMLNER) peptides; bn and yn denote the fragment ions generated by cleavage of the peptide bond after the nth amino acid containing either the N terminus (b series) or C terminus (y series), respectively.The identified peptide sequence location is shown in bold in the protein sequence.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015054&req=5

f1: MS/MS profiles of MASP-1 (YFFKDQVLVSCDTGYK) and PLTP (TMLQIGVMPMLNER) peptides; bn and yn denote the fragment ions generated by cleavage of the peptide bond after the nth amino acid containing either the N terminus (b series) or C terminus (y series), respectively.The identified peptide sequence location is shown in bold in the protein sequence.
Mentions: Among the potential biomarkers identified in our large-scale quantitative proteomic analysis, the spectral count of PLTP was >11-fold higher in AMD patients than in HCs, leading us to further investigate this protein in the current study. MASP-1 showed a less dramatic spectral count ratio of 1.13 (AMD:HC), but was also examined here owing to its relationship to signalling pathways implicated in AMD development and progression5678. Mass spectral characteristics of the two proteins are shown in Fig. 1 and the Supplementary Datasets. A western blot analysis of 12 patients randomly selected from each group revealed an upregulation of PLTP and MASP-1 expression in AMD patients relative to controls that was dependent on disease severity (Fig. 2).

View Article: PubMed Central - PubMed

ABSTRACT

Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness.

No MeSH data available.