Proteomics of thyroid tumours provides new insights into their molecular composition and changes associated with malignancy

Abstract

Around 5% of the general population have palpable thyroid nodules. Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas. Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies of large scale to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied data-independent acquisition mass spectrometry which enabled quantitative expression analysis of over 1,600 proteins from 32 specimens to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma. In follicular tumours, we found marked reduction of the tumour suppressor and therapeutic target extracellular protein decorin. We made the novel observation that TGFβ-induced protein ig-h3 (TGFBI) was found frequently overexpressed in follicular carcinoma compared with follicular adenoma. Proteomic pathway analysis showed changes in papillary carcinoma were associated with disruption of cell contacts (loss of E-cadherin), actin cytoskeleton dynamics and loss of differentiation markers, all hallmarks of an invasive phenotype.

OmixLitMiner: A Bioinformatics Tool for Prioritizing Biological Leads from ‘Omics Data Using Literature Retrieval and Data Mining

“…OmixLitMiner analysis for decorin yielded two papers and placed it in Category 2. Interestingly, both papers were published after the publication by Martinez-Aguilar et al [9], retrospectively justifying their interest in decorin. A similar finding was reported for superoxide dismutase 3 (SOD3), as two of the three reported papers were published subsequent to the Martinez-Aguilar et al [9] paper.…”

“…Interestingly, both papers were published after the publication by Martinez-Aguilar et al [9], retrospectively justifying their interest in decorin. A similar finding was reported for superoxide dismutase 3 (SOD3), as two of the three reported papers were published subsequent to the Martinez-Aguilar et al [9] paper. Another protein of particular interest to Martinez-Aguilar et al [9] was TGFBI.…”

“…For a description of the categorization terminology, see Section 4.2 in the Materials and Method section. To evaluate OmixLitMiner we first examined the data set from Martinez-Aguilar et al [9] who examined three subtypes of thyroid tumours using SWATH-MS. iTRAQ and MRM experiments were also conducted for validation. As this was an extensive, multi-group study we focused the assessment of OmixLitMiner on the differentially expressed proteins observed between normal thyroid tissue and the three tumour subtypes determined from the SWATH analysis (Supplementary Files S1-S3).…”

“…The proteins shown in Table 1 were some of the prominent ones selected by Martinez-Aguilar et al [9] for further discussion. They placed particular emphasis on decorin as this showed over 10-fold reduced levels in follicular-patterned tumour subtype compared to normal thyroid tissue.…”

Single-cell transcriptome analysis reveals cell-cell communication and thyrocyte diversity in the zebrafish thyroid gland

“…Decorin, a secreted proteoglycan, is considered a “guardian from the matrix” (36), as it is an antagonist of growth factor signaling. Importantly, Decorin expression has been reported to be downregulated in thyroid cancer samples (37). Thus, stromal cells could modulate Decorin to control thyrocytes growth.…”