Secretome-Based Identification and Characterization of Potential Biomarkers in Thyroid Cancer

Abstract

In search of thyroid cancer biomarkers, proteins secreted by thyroid cancer cell lines, papillary-derived TPC-1 and anaplastic-derived CAL62, were analyzed using liquid chromatography-tandem mass spectrometry. Of 46 high-confidence identifications, 6 proteins were considered for verification in thyroid cancer patients' tissue and blood. The localization of two proteins, nucleolin and prothymosin-α (PTMA), was confirmed in TPC-1 and CAL62 cells by confocal microscopy and immunohistochemically in xenografts of TPC-1 cells in NOD/SCID/γ mice and human thyroid cancers (48 tissues). Increased nuclear and cytoplasmic expression of PTMA was observed in anaplastic compared to papillary and poorly differentiated carcinomas. Nuclear expression of nucleolin was observed in all subtypes of thyroid carcinomas, along with faint cytoplasmic expression in anaplastic cancers. Importantly, PTMA, nucleolin, clusterin, cysteine-rich angiogenic inducer 61, enolase 1, and biotinidase were detected in thyroid cancer patients' sera, warranting future analysis to confirm their potential as blood-based thyroid cancer markers. In conclusion, we demonstrated the potential of secretome analysis of thyroid cancer cell lines to identify novel proteins that can be independently verified in cell lines, xenografts, tumor tissues, and blood samples of thyroid cancer patients. These observations support their potential utility as minimally invasive biomarkers for thyroid carcinomas and their application in management of these diseases upon future validation.

Prothymosin alpha: a ubiquitous polypeptide with potential use in cancer diagnosis and therapy

“…Cancer cell diVerentiation [50,66] Upper urinary tract Protein in tissue Tumor recurrence [59] recorded in bladder tumors compared with their normal adjacent tissues, which was most prominent in tumors of a higher grade. In upper urinary tract cancer, tumor recurrence was associated with proT overexpression, but only when the polypeptide was localized in the tumor-cell cytoplasm [59].…”

“…Indeed, soon after its identiWcation, proT was detected in human blood [64], its presence attributed either to leakage from damaged leukocytes or "secretion" from proT -rich cells via an as yet unknown mechanism. Nevertheless, to date, proT detection in cancer patients' sera is reported in only two studies (a) in breast cancer patients [65] and (b) in a secretome analysis of thyroid carcinomas [66]. Unfortunately, no correlation of blood proT levels with cancer development and/or prognosis was found.…”

FBXW7 negatively regulates ENO1 expression and function in colorectal cancer

“…1,3–5 Remarkably, accumulating evidence suggests that ENO1 can function as an oncogenic protein by promoting cell proliferation, invasion and metastasis. ENO1 expression is frequently increased in diverse tumors, including head and neck, 6 thyroid, 7 breast, 8 lung, 9,10 prostate, 11 colon and gastric cancer, 12,13 glioma 14 and cholangiocarcinoma. 15 Moreover, overexpression of ENO1 is positively associated with progression and poor prognosis in several tumors.…”

Identification of Novel Proteins Interacting with Vascular Endothelial Growth Inhibitor 174 in Renal Cell Carcinoma

“…Remarkably, accumulating evidence have suggested that ENO1 can function as an oncogenic protein by promoting cell proliferation, invasion and metastasis. ENO1 expression is frequently increased in diverse tumors, including head and neck, thyroid, breast, lung, prostate, colon and gastric cancer, glioma and cholangio carcinoma (46)(47)(48)(49). Moreover, overexpression of ENO1 is positively associated with progression and poor prognosis in several tumors (49).…”