Unveiling a novel biomarker panel for diagnosis and classification of well-differentiated thyroid carcinomas

Abstract

Thyroid cancer is the most common human endocrine malignancy with increasing global incidence. Papillary thyroid carcinomas (PTC) and follicular thyroid carcinomas (FTC) are well-differentiated thyroid cancers (WDTC) accounting for 95% of all thyroid cancer cases, with survival rates of almost 100% when diagnosed early. Since PTC and FTC have different modes of metastasis, they require different treatment strategies. Standard diagnosis by fine needle aspiration with cytopathological examination can be inaccurate in approximately 10-30% of all cases and difficult to definitively classify as WDTC. Currently, there is no single or panel of biomarkers available for thyroid cancer diagnosis and classification. This study identified novel biomarkers for thyroid cancer diagnosis and classification using proteomics, which may be translated into a biomarker panel for clinical application. Two-dimensional SDS-PAGE and mass spectrometry were used to identify potential biomarkers in papillary and follicular thyroid carcinoma cell lines, and the biomarkers were validated in five PTC and five FTC tissues, with their adjacent normal tissues from Thai patients. Eight biomarkers could distinguish PTC from normal tissues, namely enolase 1, triose phosphate isomerase, cathepsin D, annexin A2, cofilin 1, proliferating cell nuclear antigen (PCNA), copine 1 and heat shock protein 27 kDa (HSP27). These biomarkers can also discriminate FTC from normal tissues, except for annexin A2. On the contrary, annexin A2, cofilin 1, PCNA and HSP27 can be used to classify the types of WDTC. These findings have potential for use as a novel multi-marker panel for more accurate diagnosis and classification to better guide physicians on thyroid cancer treatment. Moreover, our results suggest the involvement of proteins in cell growth and proliferation, and the p53 pathway in the carcinogenesis of WDTC, which may lead to targeted therapy for thyroid cancer.

Comparative analysis of the serum proteome profiles of thyroid cancer: An initial focus on the lipid profile

“…At present, proteomics studies mainly use the techniques of matrix-assisted laser desorption ionization time-of-flight mass spectrometry and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (7). These simple methods are used to identify spectral fingerprints for prognosis and diagnosis.…”

Tumor Susceptibility Gene 101 Mediates Anoikis Resistance of Metastatic Thyroid Cancer Cells

“…Identification of key proteins involved in anoikis resistance of thyroid cancer cells. After 24 h of culture under adherent or non-adherent conditions, attached and floating ARO cells were subjected to proteomic analysis, according to the protocol in our previous study (4). Twenty-five protein spots showed significant differences in expression by more than 1.25-fold; 14 spots decreased in expression and 11 spots increased in expression in floating cells when compared to those of attached cells (Figure 2).…”

“…Initially, non-adherent culture was obtained using polyHEMA-coated plates to establish floating thyroid cancer cells (12,13). Under adherent condition (monolayer culture), BCPAP and ARO cells appeared as round-shaped epitheliallike cells, whereas FTC133 cells were elongated and fibroblast-like ( Figure 1A) (4). Under non-adherent condition, floating cells of all three cell lines aggregated into floating colonies with different aggregate densities; the colonies of BCPAP and FTC133 cells were more compact than the colonies of ATC cells ( Figure 1A).…”

“…Differential expression of spots between the two culture conditions was analyzed using ImageMaster 2D Platinum software (GE Healthcare). Protein spots with significantly differential expression greater than 1.25-fold in percent volume were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Bruker Amazon Speed ETD; Bruker, Billerica, MA, USA) and MASCOT database search, as previously described (4).…”

“…Thyroid cancer is ranked in the top ten female malignancies, with increasing worldwide incidence, as reported in 2016 (4,5). Despite early diagnosis and available effective treatments, the mortality rate has been increasing by about 0.8% annually (6).…”