iTRAQ-coupled 2D LC/MS-MS analysis of CXCR7-transfected papillary thyroid carcinoma cells: A new insight into CXCR7 regulation of papillary thyroid carcinoma progression and identification of potential biomarkers

Abstract

Abstract. Previous studies have demonstrated that C-X-C chemokine receptor type 7 (CXCR7) regulates papillary thyroid carcinoma (PTC) growth and metastasis; however, the molecular mechanisms underlying this regulation remain unclear. In the present study, the protein expression profiles of the PTC cell line GLAG-66 and GLAG-66 cells stably transfected with CXCR7 cDNA were analyzed and compared using isobaric tag for relative and absolute quantification-coupled two-dimensional liquid chromatography-tandem mass spectrometry. In total, 2,983 proteins were quantified and 130 proteins were identified to be differentially expressed, of which 87 were significantly upregulated and 43 were significantly downregulated. Gene Ontology enrichment analysis revealed that the differentially expressed proteins were primarily enriched in a number of biological processes, including metabolism-related processes, cellular component organization, transport, cellular development process and the immune response. The differentially expressed proteins identified included fibronectin 1, basigin, periplakin and serpin family B member 5, all of which are associated with cellular junctions and cancer progression. In addition, transgelin-2 and AHNAK nucleoprotein 2 were identified as potential novel biomarkers for the prognosis and treatment of PTC. IntroductionThyroid carcinoma is the most common endocrine neoplasm, of which papillary thyroid carcinoma (PTC) is the most common pathological type, accounting for 80% of thyroid carcinomas (1,2). Cervical lymph node metastasis is a typical clinical feature of PTC and is a risk factor for increased recurrence rates and decreased survival rates (3,4). Therefore, the identification of potential biomarkers that may be used to assess the prognosis and treatment of PTC is required.Chemokines and their receptors serve critical roles in the development and progression of tumors (5), particularly in promoting cell migration (6). Previous studies have demonstrated that C-X-C chemokine receptor type 7 (CXCR7) expression serves a role in tumor cell proliferation, angiogenesis, invasion and metastasis (7-10). A previous study from our laboratory demonstrated that CXCR7 was overexpressed in PTC tissue compared with peritumoral non-malignant tissue and benign thyroid lesion tissue, and the expression of CXCR7 was positively associated with cervical lymph node metastasis (11). Furthermore, knockdown of CXCR7 in PTC cells has been demonstrated to suppress cell proliferation and invasion, and promote apoptosis (12), which suggests that CXCR7 is involved in the regulation of PTC progression.In a previous study, to reveal the molecular mechanisms underlying CXCR7-mediated regulation of PTC progression, a gene microarray analysis was performed to detect changes in gene expression between PTC cells and PTC cells transfected with CXCR7. The results demonstrated that CXCR7 promotes the growth and metastasis of PTC via the activation of the phosphoinositide 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT)/nuc...

Bioinformatics analysis to screen key genes in papillary thyroid carcinoma

“…Although PTC pathogenesis has previously been reported to be associated with various biological processes (27,28), the underlying molecular mechanisms remain unclear. GO and pathway enrichment analyses of the identified DEGs demonstrated that they were primarily associated with the RNA polymerase II (Pol II) transcription coactivator, and positive regulation of cell proliferation, cell migration and extracellular exosomes.…”

Transgelin-2: Biochemical and Clinical Implications in Cancer and Asthma

“…Additionally, transgelin-2 expression is strongly upregulated in pancreatic cancer [68,69], colorectal cancer [70,71], lung adenocarcinomas [72], as well as hepatocellular carcinomas [73], uterine cervical squamous cell carcinomas [74], papillary thyroid carcinoma [75], and bladder cancers [76,77], suggesting that transgelin-2 may serve as a new biomarker to predict the progression and prognosis of cancers [13] (Table 2). More specifically, tissue microarray analyses show a positive staining rate for transgelin-2 of 85% in colorectal cancer, 50% in adenomas, and 75% in hepatic metastasis [70].…”