Biomarkers For Thyroid Cancer Research Articles

PRR15 Is a Novel Diagnostic and Prognostic Biomarker in Papillary Thyroid Cancer and Modulates the Tumor Microenvironment.

Papillary thyroid cancer (PTC), accounting for more than 80 percent of all cases of thyroid cancer, is a form of a cancerous tumor that has a very favorable prognosis. However, patients diagnosed with PTC who are already in an advanced state have a dismal outlook. This study aimed to establish the diagnostic relevance of PRR15 expression in PTC patients as well as its levels in PTC samples and its connection with immune infiltrates. The TCGA and GEO datasets were combed through to obtain information on PTC patients. The “Limma” program was used to screen for differentially expressed mRNAs (DEMs), and the results were displayed using volcano plots and heat maps. The Wilcoxon test was used to examine the level of PRR15 expression in PTC patients in comparison with that of normal tissues. To study the connection between the immune infiltration level and PRR15 expression in PTC, the single-sample sequence set enrichment analysis (ssGSEA) from the R package was utilized. The expression of PRR15 was analyzed with RT-PCR in PTC cells and normal cells. In order to evaluate the diagnostic significance of PRR15 expression, ROC assays were carried out. Experiments using CCK-8 were carried out to investigate the impact that PRR15 knockdown could have on the proliferation of PTC cells. In this study, 17 overlapped DEMs between PTC specimens and normal specimens were identified, including MPPED2, IPCEF1, SLC4A4, PKHD1L1, DIO1, CRABP1, TPO, TFF3, SPX, TCEAL2, ZCCHC12, SYTL5, PRR15, CHI3L1, SERPINA1, GABRB2, and CITED1. Our attention focused on PRR15 which was highly expressed in PTC specimens as compared with nontumor specimens. PRR15 had an AUC value of 0.926 (95% CI 0.902–0.950) for PTC based on TCGA datasets. Pan-cancer assays suggested PRR15 as an oncogenic gene in many types of tumors. Moreover, we found that PRR15 expression was positively correlated with eosinophils, NK cells, NK CD56bright cells, IDC, macrophages, DC, mast cells, and Th1 cells. Further investigations with CCK-8 demonstrated that inhibiting PRR15 resulted in a decrease in the proliferation of PTC cells. Overall, PRR15 was confirmed to be a biomarker for PTC patients and a predictor of response to immunotherapy.

Identifying key genes of classic papillary thyroid cancer in women aged more than 55 years old using bioinformatics analysis.

BackgroundThe incidence rate of thyroid carcinoma (THCA) markedly increased in the recent few decades and has been likely over-diagnosed, especially papillary thyroid cancer (PTC) in women. However, the incidence of advanced-stage papillary thyroid cancer is also rising. According to earlier studies, tumors with identical pathology might have different clinical outcomes, which implies some variances in papillary thyroid cancer. Although the mortality of thyroid cancer has remained stable or declined, there is still an important problem in estimating whether it is benign or needs surgery for patients with papillary thyroid cancer.MethodsAfter obtaining data from The Cancer Genome Atlas (TCGA) Project-THCA database by R package TCGA bio links, 18 samples (11 at stage IV as high-risk group and 7 at stage I as low-risk group) were obtained using survival package and edgeR to ensure differential expression; ClusterProfiler package was used to carry on gene set enrichment analysis and searched the possible pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. STRING and Cytoscape were used to construct and modify the protein–protein interaction (PPI) network to get hub genes of differentially expressed genes. Next, the pROC package was used to get the receiver operating characteristic (ROC) curves of hub genes’ disease-free survival (DFS). Then, transcription factors (TFs) and miRNAs of key genes were predicted by ENCORI and AnimalTFDB. In the end, TF–target genes–miRNA regulatory network was also constructed by Cytoscape.ResultsOur research obtained the top 9 candidate genes from the whole network (IFNA1, MRC1, LGALS3, LOX, POSTN, TIMP1, CD276, SDC4, and TLR2). According to the ROC results, TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN were considered to play a more critical role in malignant papillary thyroid cancer or immature cancer of papillary thyroid cancer. Our analysis concludes that TIMP1, LOX, CD276, IFNA1, TLR2, and POSTN are identified as thyroid cancer biomarkers, which lead to the different clinical courses of a woman older than 55 years old with papillary thyroid cancer. Especially CD276, POSTN, and IFNA1 may be considered as new biomarkers associated with the prognosis of thyroid cancer.ConclusionsTIMP1, LOX, CD276, IFNA1, TLR2, and POSTN have different expressions in PTCs, which lead to the various clinical courses of a woman older than 55 years old with papillary thyroid cancer. Especially CD276, POSTN, and IFNA1 may be considered as new potential biomarkers associated with the prognosis of thyroid cancer. In addition, TF–miRNA–target gene regulatory network may help further reach for PTC.

Alternative biomarkers of thyroid cancer

Serum thyroglobulin is the main biomarker for postoperative monitoring of papillary thyroid cancer recurrence however, the high prevalence of the disease dictates the need to find a reliable indicator for laboratory diagnosis of the tumor process. The presence of antibodies to thyroglobulin affects the prognosis of the disease and determines the likelihood of relapse; however, it is impossible to influence the level of antibodies using currently available methods. More commonly, trends in anti-thyroglobulin levels at the time of disease detection and after radical treatment are considered, but there is disagreement on the interpretation of the results. Currently, various alternative biomarkers are being proposed and studied, the evaluation and comparison of which will be the subject of this literature review.

Two miRNAs enriched in plasma extracellular vesicles are potential biomarkers for thyroid cancer

Differential diagnosis of thyroid cancer and benign nodules is still one of the most challenging issues in the field of endocrinology. To overcome overdiagnosis of papillary thyroid carcinomas (PTC) and the consecutive overtreatment of multinodular diseases, the search for easily accessible, sensitive and accurate biomarkers is critical. Several micro-RNAs (miRNAs) freely circulating in peripheral blood or enclosed in extracellular vesicles (EVs) have been proposed as potential biomarkers from non-invasive liquid biopsies. However, protocols are rarely comparable and conflicting data exist in the literature. In this work, we aimed to assess the diagnostic value of six micro-RNAs by comparing their expression in thyroid tissue to their abundance in bulk plasma and in plasma-EVs, before and after thyroid surgery. Plasma-EVs were isolated using a sequential density- and size-based fractionation, followed by in-depth characterization, confirming EV purity. Micro-RNA levels were measured by RT-qPCR in thyroid tissue, plasma and plasma-EVs. Among the six candidates, only miR-146b-5p and miR-21a-5p displayed a significant differential abundance in purified plasma-derived EVs from patients with PTC and benign disease. However, no difference could be demonstrated in bulk plasma through our cohort of patients. Overall, our work supports the use of a well-defined protocol of plasma-EV miRNAs purification for biomarker discovery, rather than the use of freely circulating miRNAs in bulk plasma. Our work also demonstrates that standardized pre-analytical and analytical procedures as well as optimized EV-miRNAs detection methods are essential.

Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer

BackgroundPapillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80–85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas.MethodsWe used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients’ tissues.ResultsWe identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC.ConclusionsBoth TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC.

Pro-inflammatory biomarkers in Papillary thyroid cancer

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Predictive Biomarkers in Thyroid Cancer.

In molecular pathology, predictive biomarkers identify which patients are likely to respond to targeted drugs. These therapeutic agents block specific molecules directly involved in cancer growth, dedifferentiation and progression. Until few years ago, the only targeted drugs available for advanced thyroid cancer included multi-tyrosine kinase inhibitors, mainly targeting the MAPK pathway and the angiogenic signaling. The administration of these drugs does not necessarily require a molecular characterization of tumors to assess the presence of predictive alterations. However, the availability of new selective targeted drugs for thyroid cancer patients is changing the diagnostic strategies for the molecular characterization of these tumors. The search for targetable alterations can be performed directly on tumor tissue by using a variety of methodologies, depending also on the number and type of alterations to test (i.e. single nucleotide variation or gene rearrangement). Herein, a comprehensive review of the currently available targeted treatments for thyroid cancer, related predictive markers and testing methodologies is provided.

MicroRNA-873-5p suppresses cell malignant behaviors of thyroid cancer via targeting CXCL5 and regulating P53 pathway

ABSTRACT We aimed to examine the roles of microRNA-873-5p and CXCL5 in thyroid cancer (TC) cells. qRT-PCR was adopted to measure the expression levels of CXCL5 mRNA and microRNA-873-5p in TC cells, and western blot was adopted to evaluate the CXCL5 protein expression level. Bioinformatics analysis was done to predict the upstream gene of CXCL5. Dual-luciferase assay was applied to validate the binding relationship of CXCL5 and the upstream regulatory gene. Cell experiments were done to detect the effects of microRNA-873-5p targeting CXCL5 on malignant progression of cancer cells. Western blot was adopted to demonstrate the phosphorylation level of P53 pathway related-proteins. CXCL5 was upregulated in TC cells and tissues. The results of in vitro assays displayed that CXCL5 downregulation dramatically suppressed the malignant behaviors of TC cells. MicroRNA-873-5p suppressed CXCL5 expression, but the suppressive effect of microRNA-873-5p on TC cells was abolished through CXCL5 overexpression. Additionally, microRNA-873-5p could mediate p53 pathway and thereby inhibit the malignant behaviors of TC cells through targeting CXCL5. In summary, we proved that microRNA-873-5p repressed the malignant behaviors of TC cells through targeting CXCL5 and P53 pathway, indicating that microRNA-873-5p can be a biomarker for TC.

Evaluation of the Long noncoding RNA NONHSAT037832 Gene Expression Changes in Patients with Thyroid Carcinoma

Background & Objective: Thyroid cancer is the most common endocrine disorder in the world. One of the main causes of this cancer is genetic changes, in particular mutations in the tumor and oncogene inhibition genes. In addition to mutations, some non-encoding RNAs called lncRNAs play an important role in the progression of tumors. NONHSAT is a lancer and has recently been referred to the role of this gene in various types of cancer. This study aimed to evaluate the lncRNA-NONHSAT037832 gene expression changes in patients with thyroid carcinoma.
 Materials & Methods: A cross-sectional study was conducted on 140 homogeneous samples (70 cancer tissue homogeneous samples and 70 homogeneous healthy tissue samples) from patients with thyroid cancer referred to Alzahra Hospital in Tabriz. Using the Real-Time PCR, changes in the expression of the lncRNA-NONHSAT037832 gene were evaluated. In addition, the relationship between lncRNA-NONHSAT037832 gene expression changes and clinical parameters was investigated.
 Results: The results showed that the expression of lncRNA-NONHSAT037832 gene expression in the tissues of cancer was significantly higher than healthy tissues (P <0.001) and a significant relationship with MTN (P = 0.001) and node metastasis Lymphoma was shown (P = 0.30).
 Conclusion: According to the results, the lncRNA-NONHSAT037832 gene may be used as a prognostic biomarker for thyroid cancer. 

Fluorescence Polarization Imaging of Methylene Blue Facilitates Quantitative Detection of Thyroid Cancer in Single Cells.

Simple SummaryAccurate diagnosis of thyroid fine-needle aspiration cytology is a significant clinical challenge. A method to detect thyroid cancer at the cellular level would be invaluable to reduce diagnostic uncertainty and improve clinical decision making. We studied the ability of confocal fluorescence polarization imaging of an exogenous fluorophore, methylene blue, to provide quantitative discrimination of cancerous cells in human samples. Our results indicate that fluorescence polarization imaging provides a reliable biomarker of thyroid cancer and holds the potential to shift the paradigm of cellular level cancer diagnosis from subjective visual assessment to objective measurement.Background: Diagnostic accuracy of the standard of care fine-needle aspiration cytology (FNAC) remains a significant problem in thyroid oncology. Therefore, a robust and accurate method for reducing uncertainty of cytopathological evaluation would be invaluable. Methods: In this double-blind study, we employed fluorescence emission and quantitative fluorescence polarization (Fpol) confocal imaging for sorting thyroid cells into benign/malignant categories. Samples were collected from malignant tumors, benign nodules, and normal thyroid epithelial tissues. Results: A total of 32 samples, including 12 from cytologically indeterminate categories, were stained using aqueous methylene blue (MB) solution, imaged, and analyzed. Fluorescence emission images yielded diagnostically relevant information on cytomorphology. Significantly higher MB Fpol was measured in thyroid cancer as compared to benign and normal cells. The results obtained from 12 indeterminate samples revealed that MB Fpol accurately differentiated benign and malignant thyroid nodules. Conclusions: The developed imaging approach holds the potential to provide an accurate and objective biomarker for thyroid cancer, improve diagnostic accuracy of cytopathology, and decrease the number of lobectomy and near-total thyroidectomy procedures.

Identification of Prognostic Biomarkers in Papillary Thyroid Cancer and Developing Non-Invasive Diagnostic Models Through Integrated Bioinformatics Analysis.

Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid carcinoma, mainly detected in patients with benign thyroid nodules (BTN). Due to the invasiveness of accurate diagnostic tests, there is a need to discover applicable biomarkers for PTC. So, in this study, we aimed to identify the genes associated with prognosis in PTC. Besides, we performed a machine learning tool to develop a non-invasive diagnostic approach for PTC. For the study purposes, the miRNA dataset GSE130512 was downloaded from the GEO database and then analyzed to identify the common differentially expressed miRNAs in patients with non-metastatic PTC (nm-PTC)/metastatic PTC (m-PTC) compared with BTNs. The SVM was also applied to differentiate patients with PTC from those patients with BTN using the common DEMs. A protein-protein interaction network was also constructed based on the targets of the common DEMs. Next, functional analysis was performed, the hub genes were determined, and survival analysis was then executed. A total of three common miRNAs were found to be differentially expressed among patients with nm-PTC/m-PTC compared with BTNs. In addition, it was established that the autophagosome maturation, ciliary basal body-plasma membrane docking, antigen processing as ubiquitination & proteasome degradation, and class I MHC mediated antigen processing & presentation are associated with the pathogenesis of PTC. Furthermore, it was illustrated that RPS6KB1, CCNT1, SP1, and CHD4 might serve as new potential biomarkers for PTC prognosis. RPS6KB1, CCNT1, SP1, and CHD4 may be considered new potential biomarkers used for prognostic aims in PTC. However, performing validation tests is inevitable in the future.

Circulating MicroRNA Profiles as Potential Biomarkers for Differentiated Thyroid Cancer Recurrence.

Circulating microRNAs (miRNAs) are emerging biomarkers of thyroid cancer. This study sought to identify the profile of circulating miRNAs and its response to human recombinant TSH (rhTSH) in thyroid cancer patients with recurrent/persistent disease. We obtained serum samples from 30 patients with differentiated thyroid cancer, 14 with recurrent/persistent disease and 16 with complete remission. We used next-generation sequencing to define the miRnomes along with a comprehensive quantitative PCR (qPCR) validation using 2 different platforms. We made a transversal study by comparing serum miRNA profiles of patients with or without recurrent/persistent disease and a longitudinal study looking at differences before and after rhTSH stimulation. Selected miRNAs were then studied in human thyroid cancer cell lines TPC-1, FTC-133, and OCUT-2 in response to TSH stimulation. We could not demonstrate any consistent differences in serum profiles of known miRNAs between patients with and without recurrent/persistent disease or before and after rhTSH stimulation. However, our sequencing data revealed 2 putative novel miRNAs that rise with rhTSH stimulation in the serums of patients with recurrent/persistent disease. We further confirmed by qPCR the upregulation of these putative miRNAs both in serums and in TSH-stimulated cells. We also show miRNAs that are good candidates for housekeeping genes in the serum of patients independently of the levels of TSH. The present study does not provide evidence that known miRNAs can be used as circulating markers for recurrence of thyroid cancer. However, we suggest that novel miRNA molecules may be related to thyroid cancer pathogenesis.

Abstract P148: Glycogen phosphorylase and synthase inhibitors: Novel therapeutic approaches in anaplastic thyroid cancer

Abstract Thyroid cancer (TC) is the most common endocrine cancer. Effective treatment options for papillary (PTC) and follicular (FTC) thyroid cancers afford positive patient prognoses. However, there are no effective, long-lasting treatments for anaplastic thyroid cancer (ATC), which has a median survival of five to six months. While the receptor tyrosine kinase inhibitor sorafenib can extend ATC patient survival to eleven months, tumor reoccurrence and drug resistance often develop. Therefore, there is a need for more effective targeted therapies for ATC. While the cell signaling landscape is well described in ATC, little is known about tumorigenic adaptations in ATC metabolism. Tumors exhibit an increased consumption of glucose compared to normal tissues to fuel tumor progression. Some cancers meet this high glucose requirement by storing and breaking down glycogen. While glycogen has been detected in bovine and canine thyroids, no report thus far has investigated glycogen in normal human thyroids or thyroid cancer. Therefore, our objective was to determine if normal thyroid and TC cells metabolize glycogen and to evaluate pharmacological inhibition of glycogen metabolism in ATC cells. We show for the first time that normal thyroid, PTC, FTC, and ATC cells express glycogen synthase and glycogen phosphorylase brain and liver (PYGB, PYGL) isoforms. We confirmed these observations in patient samples of normal thyroid and TC tissues via immunofluorescence. We revealed that the TC samples expressed high levels of PYGB compared to normal thyroid tissue. Electron microscopy revealed that normal thyroid cells organized glycogen in discrete glycosomes, while ATC cells exhibited smaller, dispersed glycogen packets. Importantly, we demonstrated that the glycogen synthase inhibitor guaiacol depleted glycogen content and reduced ATC cell viability. Conversely, the glycogen phosphorylase inhibitor CP-91,149 (CP) increased glycogen levels and induced apoptosis. Importantly, CP also reduced the number of stem cells in the ATC cell population. We further showed that CP synergized with sorafenib to more effectively inhibit ATC proliferation. CP enhanced glycolysis but inhibited oxidative phosphorylation as revealed using Seahorse. We confirmed an increase in glucose transporter expression using RT-qPCR and glucose import following CP treatment. This possibly represents a futile response to PYGB inhibition. We reasoned that glycogen was preferentially metabolized in ATC to fuel the pentose phosphate pathway to protect against reactive oxygen species (ROS). Indeed, we detected significantly higher levels of ROS in ATC cells treated with CP. We demonstrated that thyroid cells are able to metabolize glycogen and identified a potential biomarker for thyroid cancer (PYGB), which was targeted with CP-91,149. Our work establishes glycogen metabolism as a novel metabolic process in thyroid cells that is associated with TC dedifferentiation and provides insight to the effectiveness of inhibiting glycogen metabolism as a novel therapeutic strategy in ATC. Citation Format: Cole Davidson, Jennifer Tomczak, Eyal Amiel, Frances Carr. Glycogen phosphorylase and synthase inhibitors: Novel therapeutic approaches in anaplastic thyroid cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P148.

DIO3OS as a potential biomarker of papillary thyroid cancer

BackgroundPapillary thyroid carcinoma (PTC) is one of the common clinical tumors, where LncRNA plays an important role in tumorigenesis and its development. The purpose of this study was to explore the role of DIO3OS in PTC. MethodFirstly, this study verified the expression of DIO3OS in PTC through the public database. Then, the differences in DIO3OS expression between the PTC group and paracancerous tissues were verified using the qRT-PCR. A series of in vitro experiments were conducted to verify the function of DIO3OS in PTC, while its involvement in possible pathways was analyzed by the GSEA. The ssGSEA algorithm estimated the immune status using the queue transcriptome graph derived from the TCGA database. Further, the correlation analysis was used to confirm the relationship between DIO3OS and the immune genes. ResultThe results showed that the expression of DIO3OS was low in PTC. The same results were also confirmed by qRT-PCR analysis (P= 0.0077). In vitro, DIO3OS was localized within the cytoplasm and exosomes. Overexpression of DIO3OS hindered the proliferation, invasion, and migration of PTC cells. According to the degree of immune cell infiltration, the tumor group was divided into high immune cell infiltration group, medium immune cell infiltration group, and low immune cell infiltration group. The results showed that the DIO3OS was highly expressed in the high immune cell infiltration group (P < 0.001), which was positively correlated with the immune cell infiltration and also correlated with multiple immune genes. ConclusionIn summary, this study illustrated the expression pattern of DIO3OS in PTC, which may be involved in the immune-inflammatory pathway. Hence, our results may provide new diagnostic biomarkers and therapeutic targets for PTC.

NRXN2 Possesses a Tumor Suppressor Potential via Inhibiting the Growth of Thyroid Cancer Cells.

Thyroid cancer (THCA) is a common endocrine malignant tumor, and its global incidence of THCA has increased significantly. Neurexin 2 (NRXN2) is involved in the progression of some diseases. Nevertheless, it is still elusive towards the clinical implication and function of NRXN2 in THCA. As The Cancer Genome Atlas (TCGA) data demonstrated, we conducted a study to explore the links between NRXN2 expression and clinical features. Additionally, our data exhibited that, compared to normal thyroid tissues, NRXN2 showed low expression in THCA tissues. 20 important genes associated with NRXN2 were screened and identified. KEGG analysis data displayed that NRXN2 exhibited a link to the neuronal system, insulin secretion modulation, energy metabolism integration, muscle contraction, cardiac conduction, and neural adhesion molecule 1 (NCAM1) interactions. Our results in depth affirmed that NRXN2 was decreased in the tissues and cell lines of THCA patients. Functionally, we proved that overexpressing NRXN2 resulted in an inhibition of THCA cell proliferation, migration, and invasion in vitro. Collectively, our study demonstrated that, for the first time, NRXN2 behaved as an inhibitor of neoplasm and a promising biomarker in THCA.

Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer.

Thyroid cancer is the most common endocrine cancer. There is no systematic screening for such cancer, and the current challenge is to find potential biomarkers to facilitate an early diagnosis. Copper (Cu) and zinc (Zn) are essential micronutrients involved in the proper functioning of the thyroid gland, and changes in their concentrations have been observed in the development of cancer. Previous studies have highlighted the potential 65Cu/63Cu ratio (δ65Cu) to be a cancer biomarker. This study tests its sensitivity on plasma samples (n = 46) of Algerian patients with papillary thyroid carcinoma and a set of corresponding biopsies (n = 11). The δ65Cu ratio in blood and tumor samples was determined using multi collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), and their corresponding Cu and Zn plasma total concentrations using total reflection X-ray fluorescence (TXRF). Plasma concentrations of Cu were significantly higher (1346.1 ± 328.3 vs. 1060.5 ± 216.1 μg/L, p < 0.0001), and Zn significantly lower (942.1 ± 205.2 vs. 1027.9 ± 151.4 μg/L, p < 0.05) in thyroid cancer patients as compared to healthy controls (n = 50). Accordingly, the Cu/Zn ratio was significantly different between patients and controls (1.5 ± 0.4 vs. 1.0 ± 0.3, p < 0.0001). Furthermore, the δ65Cu plasma levels of patients were significantly lower than healthy controls (p < 0.0001), whereas thyroid tumor tissues presented high δ65Cu values. These results support the hypothesis that Cu isotopes and plasma trace elements may serve as suitable biomarkers of thyroid cancer diagnosis.

Identification of 4-methylation driven genes based prognostic signature in thyroid cancer: an integrative analysis based on the methylmix algorithm.

Thyroid cancer (TC) is known with a high rate of persistence and recurrence. We aimed to develop a prognostic signature to monitor and assess the survival of TC patients. mRNA expression and methylation data were downloaded from the TCGA database. Then, R package methylmix was applied to construct a mixed model was used to identify methylation-driven genes (MDGs) according to the methylation levels. Furthermore, an MDGs based prognostic signature and predictive nomogram were constructed according to the analysis of univariate and multivariate Cox regression. Totally 62 methylation-driven genes that were mainly enriched in substrate-dependent cell migration, cellular response to mechanical stimulus, et al. were found in TC tissues. aldolase C (AldoC), C14orf62, dishevelled 1 (DVL1), and protein tyrosine phosphatase receptor type C (PTPRC) were identified to be significantly related to patients' survival, and may serve as independent prognostic biomarkers for TC. Additionally, the prognostic methylation signature and a novel prognostic, predictive nomogram was established based on the methylation level of 4 MDGs. In this study, we developed a 4-MDGs based prognostic model, which might be the potential predictors for the survival rate of TC patients, and this findings might provide a novel sight for accurate monitoring and prognosis assessment.

Integrated Bioinformatics Analysis of DNA Methylation Biomarkers in Thyroid Cancer Based on TCGA Database.

Previous studies have reported a cluster of aberrant promoter methylation changes associated with silencing of tumor suppressor genes in thyroid cancer (TC), but these results of individual genes are far from enough. In this work, we aimed to investigate the onset and pattern of methylation changes during the progression of TC by informatics analysis. We downloaded the DNA methylation and RNA sequencing datasets from The Cancer Genome Atlas focusing on TC. Abnormally methylated differentially expressed genes (DEGs) were sorted and pathways were analyzed. The KEGG and GO were then used to perform enrichment and functional analysis of identified pathways and genes. Gene-drug interaction network and human protein atlas were applied to obtain feature DNA methylation biomarkers. In total, we identified 2170 methylation-driven DEGs, including 1054 hypermethylatedlow-expression DEGs and 1116 hypomethylated-high-expression DEGs at the screening step. Further analysis screened total of eight feature DNA methylation biomarkers (RXRG, MET, PDGFRA, FCGR3A, VEGFA, CSF1R, FCGR1A and C1QA). Pathway analysis showed that aberrantly methylated DEGs mainly associated with transcriptional misregulation in cancer, MAPK signaling, and intrinsic apoptotic signaling in TC. Taken together, we have identified novel aberrantly methylated genes and pathways linked to TC, which might serve as novel biomarkers for precision diagnosis and disease treatment.

Identifying potential metabolic tissue biomarkers for papillary thyroid cancer in different iodine nutrient regions.

To investigate the applicability of metabolomics to select thyroid cancer-associated biomarkers and discover the effects of iodine on metabolic changes in thyroid cancer. In this study, a total of 33 papillary thyroid cancer (PTC) patients from areas with iodine excess and 32 PTC patients from areas with adequate iodine were recruited, and their cancerous tissue and paracancerous tissue were collected. These specimens were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/QTOF/MS) in conjunction with multivariate statistical analysis. Good separations were obtained for PTC tissue vs. paracancerous tissue, and 15 metabolites, including L-octanoylcarnitine, N-arachidonoylglycine, and others were found to be disturbed in PTC tissue. Moreover, the metabolic profile presented considerable separation between PTC tissue from different iodine areas, and 15 metabolomic biomarkers were found to be differentially expressed. Among them, 10 metabolites, including arachidonoylcarnitine and LysoPCs, were related to thyroid cancer and excess iodine. These biomarkers play a role in arachidonic acid metabolism pathways and others. In addition, biomarkers such as 3,5-tetradecadiencarnitine and oxidized glutathione were significantly correlated with thyroid function, and biomarkers such as L-octanoylcarnitine and arachidonic acid were significantly correlated with the clinical characteristics of PTC. Distinct differences in metabolic profiles were found to exist between PTCs from areas with different levels of iodine nutrition. The identified biomarkers have significant potential for diagnosing PTC and investigating its underlying mechanisms.

Levels of Pro-inflammatory biomarkers in Papillary thyroid cancer

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)