Secretome proteins as candidate biomarkers for aggressive thyroid carcinomas

Abstract

Using proteomics in tandem with bioinformatics, the secretomes of nonaggressive and aggressive thyroid carcinoma (TC) cell lines were analyzed to detect potential biomarkers for tumor aggressiveness. A panel of nine proteins, activated leukocyte cell adhesion molecule (ALCAM/CD166), tyrosine-protein kinase receptor (AXL), amyloid beta A4 protein, amyloid-like protein 2, heterogeneous nuclear ribonucleoprotein K, phosphoglycerate kinase 1, pyruvate kinase isozyme M2, phosphatase 2A inhibitor (SET), and protein kinase C inhibitor protein 1 (14-3-3 zeta) was chosen to confirm their expression in TC patients' sera and tissues. Increased presurgical circulating levels of ALCAM were associated with aggressive tumors (p = 0.04) and presence of lymph node metastasis (p = 0.018). Increased serum AXL levels were associated with extrathyroidal extension (p = 0.027). Furthermore, differential expression of amyloid beta A4 protein, AXL, heterogeneous nuclear ribonucleoprotein K, phosphoglycerate kinase 1, pyruvate kinase muscle isozyme M2, and SET was observed in TC tissues compared to benign nodules. Decreased nuclear expression of AXL can detect malignancy with 90% specificity and 100% sensitivity (AUC = 0.995, p < 0.001). In conclusion, some of these proteins show potential for future development as serum and/or tissue-based biomarkers for TC and warrant further investigation in a large cohort of patients.

High and Low Doses of Ionizing Radiation Induce Different Secretome Profiles in a Human Skin Model

“…In this respect, tumor suppressor protein 14-3-3-σ was reported to downregulate in a radioresistant nasopharyngeal cancer cell line when compared with regular nasopharyngeal cancer cell line,[30] and the same trend was observed for non-small cell lung cancer cells in comparison with normal human bronchial epithelial cells [31]. In addition, secreted 14-3-3 zeta has been demonstrated to have potential as candidate biomarkers for aggressive thyroid carcinomas [32]. The seven 14-3-3 proteins (see Supporting Information Table S1) observed in this work all showed downregulation for all of the irradiated samples, in particular for the 200 cGy dose when compared with the sham irradiation, which showed that ionizing radiation suppress expression of many proteins within the 14-3-3 family, this may lead to perturbed homeostasis in tumor suppression and other important biological functions.…”

Proteome analysis in thyroid pathology

“…The results showed a proteomic signature specific for the ATC cells, correlated with their high proliferation rate, motility propensity and metabolic shift, in respect to the BCPAP cells. The secretome of non-aggressive and aggressive thyroid cell lines (BCPAP, SW1736 and C643) was also investigated by liquid chromatography-MS for the same purpose [100]. The expression of nine proteins was also evaluated in sera and tissue by the enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively.…”

Molecular Signature of Indeterminate Thyroid Lesions: Current Methods to Improve Fine Needle Aspiration Cytology (FNAC) Diagnosis

“…In the field of thyroid cancer, proteomics has been initially applied on thyroid tissue specimens and cancer cell lines [80,81,82,83,84,85,86,87,88,89], using different techniques such as surface-enhanced laser desorption/ionization-time-of-flight-mass spectrometry (SELDI-TOF-MS), liquid chromatography–mass spectrometry (LC/MS) and MS alone. All these studies ended by identifying specific protein signatures for malignant and benign lesions with a final selection of clusters of proteins with discriminating abilities.…”