Synergy between PEDF and Doxorubicin in Breast Cancer Cells: Effects on Metastatic and Metabolic Pathways.

Pigment epithelium-derived factor (PEDF), a serine protease inhibitor (Serpin) family member, shows promise in inhibiting tumour growth. In our study, we explored the effects of PEDF on the efficacy of the frontline chemotherapy agent doxorubicin (Dox) in BC cells. We found that Dox+PEDF treatment significantly reduced glucose uptake in MDA-MB-231 cells compared to the control (p = 0.0005), PEDF (p = 0.0137), and Dox (p = 0.0171) alone but paradoxically increased it in MCF-7 cells. Our findings further revealed that PEDF, Dox, and Dox+PEDF substantially hindered tumour cell migration from tumour spheroids, with Dox+PEDF showing the most significant impact (p < 0.0001). We also observed notable decreases in the expression of metastatic markers (uPAR, uPA, CXCR4, MT1-MMP, TNF-α) across all treatment groups (p < 0.0001) in both cell lines. When it comes to metabolic pathways, PEDF increased phosphorylated IRS-1 (p-IRS1) levels in MDA-MB-231 and MCF-7 (p < 0.0001), while Dox decreased it, and the combination led to an increase. In MDA-MB-231 cells, treatment with PEDF, Dox, and the combination led to a notable decrease in both phosphorylated AKT (p-AKT) and total AKT levels. In MCF-7, while PEDF, Dox, and their combination led to a reduction in p-AKT, total levels of AKT increased in the presence of Dox and Dox+PEDF. Combining PEDF with Dox enhances the targeting of metastatic and metabolic pathways in breast cancer cell lines. This synergy, marked by PEDF's increasing roles in cancer control, may pave the way for more effective cancer treatments.

Thyroid cancer cell metabolism: A glance into cell culture system-based metabolomics approaches.

Thyroid cancer is the most common malignancy of the endocrine system and the seventh most prevalent cancer in women worldwide. It is a complex and diverse disease characterized by heterogeneity, underscoring the importance of understanding the underlying metabolic alterations within tumor cells. Metabolomics technologies offer a powerful toolset to explore and identify endogenous and exogenous biochemical reaction products, providing crucial insights into the intricate metabolic pathways and processes within living cells. Metabolism plays a central role in cell function, making metabolomics a valuable reflection of a cell's phenotype. In the OMICs era, metabolomics analysis of cells brings numerous advantages over existing methods, propelling cell metabolomics as an emerging field with vast potential for investigating metabolic pathways and their perturbation in pathophysiological conditions. This review article aims to look into recent developments in applying metabolomics for characterizing and interpreting the cellular metabolome in thyroid cancer cell lines, exploring their unique metabolic characteristics. Understanding the metabolic alterations in tumor cells can lead to the identification of critical nodes in the metabolic network that could be targeted for therapeutic intervention.

The Impact of Pigment-Epithelium-Derived Factor on MCF-7 Cell Metabolism in the Context of Glycaemic Condition.

Studies have demonstrated that pigment-epithelium-derived factor (PEDF) is a robust inhibitor of tumour growth and development, implying that this may serve as a promising target for therapeutic intervention. However, the precise impact of PEDF on cancerous cell metabolic pathways remains uncertain despite ongoing research. In this light, this study aimed to employ a metabolomics approach for understanding the metabolic reprogramming events in breast cancer across different glycaemic loads and their response to PEDF. Gas chromatography-quadrupole mass spectrometry (GC/Q-MS) analysis revealed metabolic alterations in ER+ human cell line MCF-7 cells treated with PEDF under varying glycaemic conditions. The identification of significantly altered metabolites was accomplished through MetaboAnalyst (v.5.0) and R packages, which enabled both multivariate and univariate analyses. Out of the 48 metabolites identified, 14 were chosen based on their significant alterations in MCF-7 cells under different glycaemic conditions and PEDF treatment (p < 0.05, VIP > 0.8). Dysregulation in pathways associated with amino acid metabolism, intermediates of the TCA cycle, nucleotide metabolism, and lipid metabolism were detected, and they exhibited different responses to PEDF. Our results suggest that PEDF has a diverse influence on the metabolism of MCF-7 cells in both normo- and hyperglycaemic environments, thereby warranting studies using patient samples to correlate our findings with clinical response in the future.

Deciphering molecular mechanisms of SARS-CoV-2 pathogenesis and drug repurposing through GRN motifs: a comprehensive systems biology study.

The world has recently been plagued by a new coronavirus infection called SARS-CoV-2. This virus may lead to severe acute respiratory syndrome followed by multiple organ failure. SARS-CoV-2 has approximately 80-90% genetic similarity to SARS-CoV. Given the limited omics data available for host response to the viruses (more limited data for SARS-CoV-2), we attempted to unveil the crucial molecular mechanisms underlying the SARS-CoV-2 pathogenesis by comparing its regulatory network motifs with SARS-CoV. We also attempted to identify the non-shared crucial molecules and their functions to predict the specific mechanisms for each infection and the processes responsible for their different manifestations. Deciphering the crucial shared and non-shared mechanisms at the molecular level and signaling pathways underlying both diseases may help shed light on their pathogenesis and pave the way for other new drug repurposing against COVID-19. We constructed the GRNs for host response to SARS-CoV and SARS-CoV-2 pathogens (in vitro) and identified the significant 3-node regulatory motifs by analyzing them topologically and functionally. We attempted to identify the shared and non-shared regulatory elements and signaling pathways between their host responses. Interestingly, our findings indicated that NFKB1, JUN, STAT1, FOS, KLF4, and EGR1 were the critical shared TFs between motif-related subnetworks in both SARS and COVID-1, which are considered genes with specific functions in the immune response. Enrichment analysis revealed that the NOD-like receptor signaling, TNF signaling, and influenza A pathway were among the first significant pathways shared between SARS and COVID-19 up-regulated DEGs networks, and the term "metabolic pathways" (hsa01100) among the down-regulated DEGs networks. WEE1, PMAIP1, and TSC22D2 were identified as the top three hubs specific to SARS. However, MYPN, SPRY4, and APOL6 were the tops specific to COVID-19 in vitro. The term "Complement and coagulation cascades" pathway was identified as the first top non-shared pathway for COVID-19 and the MAPK signaling pathway for SARS. We used the identified crucial DEGs to construct a drug-gene interaction network to propose some drug candidates. Zinc chloride, Fostamatinib, Copper, Tirofiban, Tretinoin, and Levocarnitine were the six drugs with higher scores in our drug-gene network analysis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03518-x.

Metabolomics Profiling Reveals the Role of PEDF in Triple-Negative Breast Cancer Cell MDA-MB-231 under Glycaemic Loading.

Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein that belongs to the serine protease inhibitor (serpin) family. An increase in PEDF activity has been shown to be a potent inhibitor of tumour progression and proliferation, suggesting a possible therapeutic target. There is still a great deal to learn about how PEDF controls metabolic pathways in breast cancer and its metastatic form. Given this, the primary purpose of this study was to use a metabolomics approach to gain a better understanding of the mechanisms driving the reprogramming of metabolic events involved in breast cancer pertaining to PEDF under various glycaemic loads. We employed gas chromatography-quadrupole mass spectrometry (GC-Q-MS) to investigate metabolic changes in the triple-negative breast cancer (TNBC) cell line MDA-MB-231 treated with PEDF under glycaemic loading. Multivariate and univariate analyses were carried out as indicative tools via MetaboAnalyst (V.5.0) and R packages to identify the significantly altered metabolites in the MDA-MB-231 cell line after PEDF exposure under glycaemic loading. A total of 61 metabolites were found, of which nine were selected to be distinctively expressed in MDA-MB-231 cells under glycaemic conditions and exhibited differential responses to PEDF (p < 0.05, VIP > 1). Abnormalities in amino acid metabolism pathways were observed. In particular, glutamic acid, glutamine, and phenylalanine showed different levels of expression across different treatment groups. The lactate and glucose-6-phosphate production significantly increased in high-glucose vs. normal conditions while it decreased when the cells were exposed to PEDF, confirming the positive influence on the Warburg effect. The TCA cycle intermediates, including malate and citric acid, showed different patterns of expression. This is an important finding in understanding the link of PEDF with metabolic perturbation in TNBC cells in response to glycaemic conditions. Our findings suggest that PEDF significantly influenced the Warburg effect (as evidenced by the significantly lower levels of lactate), one of the well-known metabolic reprogramming pathways in cancer cells that may be responsive to metabolic-targeted therapeutic strategies. Moreover, our results demonstrated that GC-MS-based metabolomics is an effective tool for identifying metabolic changes in breast cancer cells after glycaemic stress or in response to PEDF treatment.

Elevated Plasma Levels of MT4-MMP and MT6-MMP; A New Observation in Patients with Thyroid Nodules.

BACKGROUND: Based on the critical role of MT4-MMP and MT6-MMP in carcinogenesis, we focused on MT4-MMP and MT6-MMP circulating levels in patients with thyroid nodules. METHODS: Plasma samples were collected from three groups, including papillary thyroid cancer (PTC; n=30), multinodular goiter (MNG; n=30), and healthy subjects (n=22). Enzyme-linked immunosorbent assay (ELISA) was used to obtain the concentration of MT4-MMP and MT6-MMP in the three groups. RESULTS: Analysis of data demonstrated increased levels of MT4-MMP (PTC: 4.90±1.35, MNG: 4.89±1.37, and healthy: 3.13±1.42) and MT6-MMP (PTC: 8.29±2.50, MNG: 7.34±2.09, and healthy:5.01±2.13) in thyroid nodules by comparison with healthy subjects (P<0.05). There were no significant differences in the levels of the two MT-MMPs between PTC and MNG (P>0.05). Increased plasma levels of MT4-MMP (odds ratio=2.48; 95% CI: 1.46-4.19; P=0.001) or MT6-MMP (odds ratio=1.81; 95% CI: 1.29-2.53; P=0.001) were associated with increased risk of PTC tumorigenesis. Interestingly, a strong positive association was observed between MT4-MMP and MT6-MMP in the three groups (PTC: r=0.766**, P=0.000; MNG: r=0.856**, P=0.000; healthy r=0.947**, P=0.000). Areas under the ROC curve for MT4-MMP and MT6-MMP were 0.82 and 0.96, respectively. At the cutoff value>4.7 (ng/mL), MT4-MMP and MT6-MMP showed a sensitivity of 63.3% and 90.0%, respectively, with 100% specificity. CONCLUSION: Our work has led us to imply that the higher levels of MT4-MMP and MT6-MMP are closely linked with both PTC and MNG tumorigenesis. They may probably promote the development of thyroid lesions; however, more research is needed to further clarify the current findings.

Metabolomics-A Tool to Find Metabolism of Endocrine Cancer.

Clinical endocrinology entails an understanding of the mechanisms involved in the regulation of tumors that occur in the endocrine system. The exact cause of endocrine cancers remains an enigma, especially when discriminating malignant lesions from benign ones and early diagnosis. In the past few years, the concepts of personalized medicine and metabolomics have gained great popularity in cancer research. In this systematic review, we discussed the clinical metabolomics studies in the diagnosis of endocrine cancers within the last 12 years. Cancer metabolomic studies were largely conducted using nuclear magnetic resonance (NMR) and mass spectrometry (MS) combined with separation techniques such as gas chromatography (GC) and liquid chromatography (LC). Our findings revealed that the majority of the metabolomics studies were conducted on tissue, serum/plasma, and urine samples. Studies most frequently emphasized thyroid cancer, adrenal cancer, and pituitary cancer. Altogether, analytical hyphenated techniques and chemometrics are promising tools in unveiling biomarkers in endocrine cancer and its metabolism disorders.

CpG island status as an epigenetic alteration for NIS promoter in thyroid neoplasms; a cross-sectional study with a systematic review.

BACKGROUND: Gene silence via methylation of the CpG islands is cancer's most common epigenetic modification. Given the highly significant role of NIS in thyroid cancer (TC) differentiation, this cross-sectional study aimed to investigate the DNA methylation pattern in seven CpG islands (CpG1-7 including +846, +918, +929, +947, +953, +955, and +963, respectively) of the NIS promoter in patients diagnosed with papillary (PTC), follicular (FTC), and multinodular goiter (MNG). Additionally, a systematic review of the literature was conducted to compare our results with studies concerning methylation of the NIS gene promoter. METHODS: Thyroid specimens from 64 patients met the eligibility criteria, consisting of 28 PTC, 9 FTC, and 27 benign MNG cases. The mRNA of NIS was tested by qRT-PCR. The bisulfite sequencing PCR (BSP) technique was performed to evaluate the promoter methylation pattern of the NIS gene. Sequencing results were received in chromatograph, FASTA, SEQ, and pdf formats and were analyzed using Chromas. The methylation percentage at each position and for each sample was calculated by mC/(mC+C) formula for all examined CpGs; following that, the methylation percentage was also calculated at each CpG site. Besides, a literature search was conducted without restricting publication dates. Nine studies met the eligibility criteria after removing duplicates, unrelated articles, and reviews. RESULTS: NIS mRNA levels decreased in tumoral tissues of PTC (P = 0.04) and FTC (P = 0.03) patients compared to their matched non-tumoral ones. The methylation of NIS promoter was not common in PTC samples, but it was frequent in FTC (P < 0.05). Significant differences were observed in the methylation levels in the 4th(+ 947), 6th(+ 955), and 7th(+ 963) CpGs sites in the forward strand of NIS promoter between FTC and MNG tissues (76.34 ± 3.12 vs 40.43 ± 8.42, P = 0.004, 69.63 ± 3.03 vs 23.29 ± 6.84, P = 0.001 and 50.33 ± 5.65 vs 24 ± 6.89, P = 0.030, respectively). There was no significant correlation between the expression and methylation status of NIS in PTC and FTC tissues. CONCLUSION: Perturbation in NIS promoter's methylation individually may have a potential utility in differentiating MNG and FTC tissues. The absence of a distinct methylation pattern implies the importance of other epigenetic processes, which may alter the production of NIS mRNA. In addition, according to the reversibility of DNA methylation, it is anticipated that the design of particular targeted demethylation medicines will lead to a novel cancer therapeutic strategy.

Looking at Thyroid Cancer from the Tumor-Suppressor Genes Point of View.

Thyroid cancer is the most frequent endocrine malignancy and accounts for approximately 1% of all diagnosed cancers. A variety of mechanisms are involved in the transformation of a normal tissue into a malignant one. Loss of tumor-suppressor gene (TSG) function is one of these mechanisms. The normal functions of TSGs include cell proliferation and differentiation control, genomic integrity maintenance, DNA damage repair, and signaling pathway regulation. TSGs are generally classified into three subclasses: (i) gatekeepers that encode proteins involved in cell cycle and apoptosis control; (ii) caretakers that produce proteins implicated in the genomic stability maintenance; and (iii) landscapers that, when mutated, create a suitable environment for malignant cell growth. Several possible mechanisms have been implicated in TSG inactivation. Reviewing the various TSG alteration types detected in thyroid cancers may help researchers to better understand the TSG defects implicated in the development/progression of this cancer type and to find potential targets for prognostic, predictive, diagnostic, and therapeutic purposes. Hence, the main purposes of this review article are to describe the various TSG inactivation mechanisms and alterations in human thyroid cancer, and the current therapeutic options for targeting TSGs in thyroid cancer.

Gas chromatography-mass spectrometry-based untargeted metabolomics reveals metabolic perturbations in medullary thyroid carcinoma.

Medullary thyroid cancer (MTC) is a rare tumor that arises from parafollicular cells within the thyroid gland. The molecular mechanism underlying MTC has not yet been fully understood. Here, we aimed to perform plasma metabolomics profiling of MTC patients to explore the perturbation of metabolic pathways contributing to MTC tumorigenesis. Plasma samples from 20 MTC patients and 20 healthy subjects were obtained to carry out an untargeted metabolomics by gas chromatography-mass spectrometry. Multivariate and univariate analyses were employed as diagnostic tools via MetaboAnalyst and SIMCA software. A total of 76 features were structurally annotated; among them, 13 metabolites were selected to be differentially expressed in MTC patients compared to controls (P < 0.05). These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids and amino acid metabolisms, mostly leucine, glutamine, and glutamate, tightly responsible for tumor cells' energy production. Moreover, according to the receiver operating characteristic curve analysis, metabolites with the area under the curve (AUC) value up to 0.90, including linoleic acid (AUC = 0.935), linolenic acid (AUC = 0.92), and leucine (AUC = 0.948) could discriminate MTC from healthy individuals. This preliminary work contributes to existing knowledge of MTC metabolism by providing evidence of a distinctive metabolic profile in MTC patients relying on the metabolomics approach.

The relation of omentin gene expression and glucose homeostasis of visceral and subcutaneous adipose tissues in non-diabetic adults.

BACKGROUND: Adipose tissue (AT) is a passive reservoir for energy storage and an active endocrine organ responsible for synthesizing bioactive molecules called adipokines. Omentin is known as an anti-inflammatory adipokine that can modulate insulin sensitivity. The present study aimed to investigate the relationship between omentin mRNA expression and glucose homeostasis of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in non-diabetic adults. METHODS: VAT and SAT adipose tissues were collected from 137 adults aged ≥ 18 years hospitalized for abdominal surgery. Before surgery, preoperative blood samples were taken from the participants to measure fasting plasma glucose, insulin, and triglyceride. BMI, HOMA-IR, HOMA-B, and QUICKI were calculated. Insulin levels were measured with Mercodia kits using enzyme-linked immunosorbent assay (ELISA). In order to obtain omentin mRNA expression, real-time PCR was performed. RESULTS: Overall, 91 (66.4%) subjects were healthy [without insulin resistance (IR)], and 46 (33.6%) participants were with IR. In healthy and IR subjects, omentin gene expression was 1.04 and 2.32, respectively in VAT, and 3.06 and 1.30, respectively, in SAT (P > 0.05). After controlling for age and BMI, linear regression analysis indicated a significant positive association of SAT omentin expression with insulin concentration (ß = 0.048; 95% CI 0.009, 0.088, P = 0.017) and HOMA-IR (ß = 0.173; 95% CI 0.023, 0.323, P = 0.014). Moreover, a negative association of SAT omentin expression with HOMA-B (ß = - 0.001; 95% CI 0.002, - 0.001, P < 0.001) was observed. CONCLUSION: This study's finding confirms a direct association between IR with omentin mRNA levels in SAT. Besides, the indicator of insulin sensitivity had an inverse association with omentin gene expression in SAT. This aspect of research suggests that omentin secretion from SAT has a strong link with insulin regulation.

The increasing role of pigment epithelium-derived factor in metastasis: from biological importance to a promising target.

Pigment epithelium-derived factor (PEDF) is a non-inhibitory member of the serpin (serine protease inhibitor) family and is a well-known potent anti-tumor factor in a variety of cancers. It has been ascertained that PEDF regulates multiple metastatic processes through various plausible mechanisms, including inhibiting angiogenesis, inducing apoptosis, stimulating extracellular matrix (ECM) degradation, and suppressing the epithelial-to-mesenchymal transition (EMT) process. Although PEDF has been recognized as an anti-metastatic marker in most studies, its role remains controversial with conflicting reports of PEDF as a metastatic marker. The emerging insights into the mechanism(s) of PEDF in tumor progression and its therapeutic effects are discussed systematically in this review, aiming to improve our understanding in the context of metastasis and drug development.

A glance at the actual role of glutamine metabolism in thyroid tumorigenesis.

Thyroid cancers (TCs) are the most prevalent malignancy of the endocrine system and the seventh most common cancer in women. According to estimates from the Global Cancer Observatory (GCO) in 2020, the incidence of thyroid cancer globally was 586,000 cases. As thyroid cancer incidences have dramatically increased, identifying the most important metabolic pathways and biochemical markers involved in thyroid tumorigenesis can be critical strategies for controlling the prevalence and ultimately treatment of this disease. Cancer cells undergo cellular metabolism and energy alteration in order to promote cell proliferation and invasion. Glutamine is one of the most abundant free amino acids in the human body that contributes to cancer metabolic remodeling as a carbon and nitrogen source to sustain cell growth and proliferation. In the present review, glutamine metabolism and its regulation in cancer cells are highlighted. Thereafter, emphasis is given to the perturbation of glutamine metabolism in thyroid cancer, focusing on metabolomics studies.

The biological relevance of pigment epithelium-derived factor on the path from aging to age-related disease.

Pigment epithelium-derived factor (PEDF) is an endogenously produced protein that contributes to cell growth arrest, and reduced levels of PEDF are associated with the progression of cellular senescence and the aging process. However, the mechanisms underlying PEDF regulation of these events are not completely clear. Increased PEDF activity may induce anti-aging processes, suggesting the potential therapeutic value of PEDF as an anti-aging and age-related disease. In this review, we recapitulate the molecular and cellular mechanisms of aging following the characteristics and specific roles of the PEDF in cell cycle arrest and its relevance to cellular senescence and aging pathways. In this context, the discovery and fluctuations of PEDF in age-related diseases are summarised. In light of the importance of PEDF in cellular senescence and aging processes, better comprehension of the mechanism(s) of PEDF in the regulation of cell cycle and the aging process can conceivably facilitate the development of therapeutic strategies for diseases that occur with aging.

Low level of plasma fibulin-1 in patients with thyroid lesions: a case-control study and literature review.

Investigating novel biomarkers discriminating thyroid nodules is a matter of great importance for differential diagnosis. The current study was planned to investigate the diagnostic value of fibulin-1 in plasma specimens of patients with thyroid nodules. A literature review was also performed to gain an understanding of the existing research relevant to the main role of fibulin-1 in carcinogenesis. In this case-control study, the levels of plasma fibulin-1 were compared in 82 subjects including papillary thyroid cancer (PTC; n = 30), multinodular goiter (MNG; n = 30), and healthy subjects (n = 22) using enzyme-linked immunosorbent assay (ELISA). Fibulin-1 levels of patients with PTC and MNG were documented to be significantly lower than those of healthy subjects (PTC vs. Healthy; P = 0.000, MNG vs. Healthy; P = 0.000). No statistically significant differences were found between PTC and MNG groups when fibulin-1 levels were compared (P > 0.05). Low level of plasma fibulin-1 was associated with an increased risk of PTC tumorigenesis (odds ratio = 0.810; 95% CI: 0.704-0.933; P = 0.003). Further, fibulin-1 had an appropriate diagnostic value for detecting PTC patients with a sensitivity of 73.33%, and specificity of 100% at the cutoff value > 4.9 (ng/ml). According to the results of the present research which are tied well with previous studies, the abnormal downregulation of fibulin-1 may play a role in the PTC and MNG tumorigenesis. In addition, fibulin-1 probably promotes the development and progression of other human cancer; however, further studies are needed to improve current understandings.

Plasma Metabolic Profiling of Human Thyroid Nodules by Gas Chromatography-Mass Spectrometry (GC-MS)-Based Untargeted Metabolomics.

One of the challenges in the area of diagnostics of human thyroid cancer is a preoperative diagnosis of thyroid nodules with indeterminate cytology. Herein, we report an untargeted metabolomics analysis to identify circulating thyroid nodule metabolic signatures, to find new novel metabolic biomarkers. Untargeted gas chromatography-quadrupole-mass spectrometry was used to ascertain the specific plasma metabolic changes of thyroid nodule patients, which consisted of papillary thyroid carcinoma (PTC; n = 19), and multinodular goiter (MNG; n = 16), as compared to healthy subjects (n = 20). Diagnostic models were constructed using multivariate analyses such as principal component analysis, orthogonal partial least squares-discriminant analysis, and univariate analysis including One-way ANOVA and volcano plot by MetaboAnalyst and SIMCA software. Because of the multiple-testing issue, false discovery rate p-values were also computed for these functions. A total of 60 structurally annotated metabolites were subjected to statistical analysis. A combination of univariate and multivariate statistical analyses revealed a panel of metabolites responsible for the discrimination between thyroid nodules and healthy subjects, with variable importance in the projection (VIP) value greater than 0.8 and p-value less than 0.05. Significantly altered metabolites between thyroid nodules versus healthy persons are those associated with amino acids metabolism, the tricarboxylic acid cycle, fatty acids, and purine and pyrimidine metabolism, including cysteine, cystine, glutamic acid, α-ketoglutarate, 3-hydroxybutyric acid, adenosine-5-monophosphate, and uracil, respectively. Further, sucrose metabolism differed profoundly between thyroid nodule patients and healthy subjects. Moreover, according to the receiver operating characteristic (ROC) curve analysis, sucrose could discriminate PTC from MNG (area under ROC curve value = 0.92). This study enhanced our understanding of the distinct metabolic pathways associated with thyroid nodules, which enabled us to distinguish between patients and healthy subjects. In addition, our study showed extensive sucrose metabolism in the plasma of thyroid nodule patients, which provides a new metabolic signature of the thyroid nodule's tumorigenesis. Accordingly, it suggests that sucrose can be considered as a circulating biomarker for differential diagnosis between malignancy and benignity in indeterminate thyroid nodules.

Advances in metabolomics of thyroid cancer diagnosis and metabolic regulation.

Thyroid cancers (TCs) are the most frequent endocrine malignancy with an unpredictable fast-growing incidence, especially in females all over the world. Fine-needle aspiration biopsy (FNAB) analysis is an accurate diagnostic method for detecting thyroid nodules and classification of TC. Though simplicity, safety, and accuracy of FNAB, 15-30% of cases are indeterminate, and it is not possible to determine the exact cytology of the specimen. This demands the need for innovative methods capable to find crucial biomarkers with adequate sensitivity for diagnosis and prediction in TC researches. Cancer-based metabolomics is a vast emerging field focused on the detection of a large set of metabolites extracted from biofluids or tissues. Using analytical chemistry procedures allows for the potential recognition of cancer-based metabolites for the purposes of advancing the era of personalized medicine. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) coupled with separation techniques e.g., gas chromatography (GC) and liquid chromatography (LC) are the main approaches for metabolic studies in cancers. The immense metabolite profiling has provided a chance to discover novel biomarkers for early detection of thyroid cancer and reduce unnecessary aggressive surgery. In this review, we recapitulate the recent advances and developed methods of diverse metabolomics tools and metabolic phenotypes of thyroid cancer, following a brief discussion of recent challenges in the thyroid cancer diagnosis.

Lack of Association between Serum Adiponectin/Leptin Levels and Medullary Thyroid Cancer.

BACKGROUND: Adipokines are bioactive proteins that mediate metabolism, inflammation and angiogenesis. Changes in the secretion of key serum adipokines - adiponectin and letpin - may be associated with obesity, cancer and metabolic disorders. Thyroid cancer is one of the most important types of endocrine cancer. Therefore, investigating the association between serum levels of adiponectin and leptin and thyroid cancer might be important. The purpose of this study was to assess adiponectin and leptin levels in medullary thyroid carcinoma (MTC) cases in order to identify novel tumor markers. MATERIALS AND METHODS: This research was based on a case-control study, including 45 patients with medullary thyroid cancer (21 men and 24 women) and 45 healthy controls (24 males and 21 females). Adiponectin and leptin levels were measured by ELISA in both groups. Height and weight were measured and body mass index (kg/m2) was calculated. RESULTS: Adiponectin and leptin levels were not significantly different between medullary thyroid carcinomas and the control group. Also, there was no correlation among age and body mass index and the disease. CONCLUSIONS: These results suggest that changes in serum adiponectin and leptin levels do not play an important role in the diagnosis or could act as as biomarkers for medullary thyroid cancer.