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. 2022 Jul 28:13:923465.
doi: 10.3389/fendo.2022.923465. eCollection 2022.

Proteomic profiling of thyroid tissue in patients with obesity and benign diffuse goiter

Hicham Benabdelkamel  1 , Mohamed Rafiullah  2 , Afshan Masood  1 , Abdulaziz Alsaif  3 , Mohthash Musambil  1 , Assim A Alfadda  1   2   4
Affiliations

Proteomic profiling of thyroid tissue in patients with obesity and benign diffuse goiter

Hicham Benabdelkamel et al. Front Endocrinol (Lausanne). .

Abstract

Goiter is a term to describe the enlargement of the thyroid gland. The pathophysiology and molecular changes behind development of diffuse benign goiter remains unclear. The present study targeted to identify and describe the alterations in the thyroid tissue proteome from patients (obese euthyroid) with benign diffuse goiter (BDG) using proteomics approach. Thyroid tissue samples, from 7 age and sex matched, patients with BDG and 7 controls were obtained at the time of surgery. An untargeted proteomic analysis of the thyroid tissue was performed out utilizing two-dimensional difference (2D-DIGE) in gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for identification of the proteins. Progenesis software was used to identify changes in expression of tissue proteins and found statistically significant differences in abundance in a total of 90 proteins, 46 up and 44 down (1.5-fold change, ANOVA, p ≤ 0.05) in BDG compared to the control group. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of signalling pathways linked to ERK1/2, Glutathione peroxidase and NADPH oxidase associated to organismal injury and abnormalities, endocrine system disorders and cancer. The thyroid tissue proteome in patients with BDG revealed a significant decrease in thyroglobulin along with dysregulation of glycolysis and an increase in prooxidant peroxidase enzymes. Dysregulation of metabolic pathways related to glycolysis, redox proteins, and the proteins associated with maintaining the cytoskeletal structure of the thyrocytes was also identified.

Keywords: 2D-DIGE; MALDI-TOF; goiter; obese; proteomics; thyroid tissue.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be considered as a potential conflict of interest.

Figures

Figure 1
Figure 1
Representative fluorescent protein profile of a 2D-DIGE comprising tissue samples from BDG patients labelled with Cy3 (A), Cy5 (B), pooled internal control labelled with Cy2 (C), and merged image (D).
Figure 2
Figure 2
The two first principle components are plotted on a PCA. Together, they explained 82 percent of the variability in the chosen spot. Gels and spots are represented as colored dots and numerals, respectively.
Figure 3
Figure 3
Expression profiles divided into expression pattern clusters, with the number of spots for each cluster indicated. Each line indicates a spot’s standardized abundance covering all gels and corresponds to one among the clusters created by hierarchical cluster analysis. The spots with increased abundance indicate the 46 proteins up regulated (A). The spots with decreased abundance indicate the 44 proteins downregualted in thyroid tissue from patients with BDG compared to control states (B) (Progenesis SameSpots).
Figure 4
Figure 4
The most enriched interaction network of the differentially expressed proteins in BDG compared to the control thyroid states. Red nodes indicate up-regulated; green nodes indicate down-regulated. The central nodes in th the pathway related to signaling of the ERK1/2, Glutathione peroxidase and NADPH oxidase were found to be deregulated between the two groups. Uncolored nodes indicate potential targets that were functionally matched with the differentially expressed proteins. Solid lines indicates direct molecular connections, whereas dashed lines denotes indirect interactions (A). The figure depicts the top 15 canonical pathways as graded by the IPA’s P-values (B).
Figure 5
Figure 5
Comparative representation (percentage) of identified proteins divided into groups based on their Molecular function (A) and Biological process (B).
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