Identification of novel biomarker and therapeutic target candidates for diagnosis and treatment of follicular carcinoma

Abstract

Distinguishing follicular carcinoma from follicular adenoma, based on cytomorphological features, has always been challenging to cytopathologists. Identification of biomarkers for improving diagnostic accuracy is important for clinical management. Meanwhile, it is critical to identify therapeutic target candidates for treatment of follicular carcinoma. Currently, no reliable diagnostic protein biomarkers and therapeutic targets are available. To explore novel protein biomarker and therapeutic target candidates, a liquid chromatography-tandem mass spectrometry approach was applied to analyze control, follicular adenoma, and follicular carcinoma using formalin-fixed, paraffin-embedded tissue samples. The proteomics analysis revealed 80 protein biomarker candidates for diagnosis of thyroid follicular carcinoma. The candidates were prioritized into three categories and ranked within each category. Using the proteomics data and bioinformatics results, the top seven biomarker candidates were coiled-coil-helix-coiled-coil-helix domain-containing protein 2, mitochondrial (CHCHD2), succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrial (SUCLG2), stomatin-like protein 2, mitochondrial (STOML2), ES1 protein homolog, mitochondrial (C21orf33), fumarate hydratase, mitochondrial (FH), 3-hydroxyacyl-CoA dehydrogenase type-2 (HSD17B10), and electron transfer flavoprotein subunit beta (ETFB); and the top seven therapeutic target candidates were insulin receptor (INSR), Myc proto-oncogene protein (MYC), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), gastrin (GAST), N-myc proto-oncogene protein (MYCN), transforming growth factor beta-1 (TGFB1), and interleukin-4 (IL4). Immunohistochemical staining of SUCLG2 and ETFB is highly consistent with the discovery of proteomics, revealing that SUCLG2 has a sensitivity of 75% and a specificity of 80% to distinguish follicular carcinoma from follicular adenoma based on a specific cut-off score calculated from the IHC staining percentage and intensity. Biological significanceDistinguishing follicular carcinoma from follicular adenoma, based on cytomorphological features, has always been challenging to cytopathologists. Fourteen biomarker candidates were identified. Two of them were validated with Immunohistochemical staining. The Identification of biomarkers for improving diagnostic accuracy is important for clinical management.