The Protein Network in Subcutaneous Fat Biopsies from Patients with AL Amyloidosis: More Than Diagnosis?

Abstract

AL amyloidosis is caused by the misfolding of immunoglobulin light chains leading to an impaired function of tissues and organs in which they accumulate. Due to the paucity of -omics profiles from undissected samples, few studies have addressed amyloid-related damage system wide. To fill this gap, we evaluated proteome changes in the abdominal subcutaneous adipose tissue of patients affected by the AL isotypes κ and Λ. Through our retrospective analysis based on graph theory, we have herein deduced new insights representing a step forward from the pioneering proteomic investigations previously published by our group. ECM/cytoskeleton, oxidative stress and proteostasis were confirmed as leading processes. In this scenario, some proteins, including glutathione peroxidase 1 (GPX1), tubulins and the TRiC complex, were classified as biologically and topologically relevant. These and other results overlap with those already reported for other amyloidoses, supporting the hypothesis that amyloidogenic proteins could induce similar mechanisms independently of the main fibril precursor and of the target tissues/organs. Of course, further studies based on larger patient cohorts and different tissues/organs will be essential, which would be a key point that would allow for a more robust selection of the main molecular players and a more accurate correlation with clinical aspects.

Differentially Expressed Genes, miRNAs and Network Models: A Strategy to Shed Light on Molecular Interactions Driving HNSCC Tumorigenesis

“…The diameter, average distance, degree, betweenness, centroid, stress, eigenvector, bridging, eccentricity, closeness, radiality and edge centralities were calculated. Nodes with betweenness, centroid and bridging values above the average calculated from the whole reference network were considered hubs as previously reported [ 50 ]. The statistical significance of the topological results was tested by randomized network models [ 51 ]; n = 1000 random models per group were reconstructed and analyzed by in house R scripts based on VertexSort (to build random models), igraph (to compute centralities) and ggplot2 (to plot results) libraries.…”

Enhancing neovascularization post-myocardial infarction through injectable hydrogel functionalized with endothelial-derived EVs

“…Data Processing: the experimental tandem mass spectra (MS/MS) were matched against the insilico tryptic peptide sequences from the Homo sapiens protein database retrieved from UNIPROT (www.uniprot.org) in June 2022. Data processing was performed by Proteome Discoverer 2.5 software (Thermo Fisher Scientific), as previously reported [29].…”

“…Label-free quantitation and protein-protein interaction (PPI) network analysis: the peptide spectrum match values of the identified proteins were normalized using a total signal normalization method and compared using a label-free quantification approach, as previously reported [29]. Proteins selected by LDA were processed by hierarchical clustering applying Ward's method and a Euclidean distance metric using JMP15.2 software.…”