Biomarkers For Thyroid Cancer Research Articles

Tumor desmoplasia outperforms preoperative serum calcitonin as surgical biomarker in sporadic medullary thyroid cancer

AbstractBackgroundConceptually, thyroid tumor desmoplasia may be better suited for excluding node metastases in sporadic MTC than preoperative serum calcitonin levels.MethodsThis analysis included 181 patients with unilateral sporadic MTC graded on the 7‐grade desmoplasia scale after thyroidectomy and neck dissection.ResultsWhen thyroid tumor desmoplasia reached 1% and ≥50%, node metastases increased from 0% to 7% (median of 0 metastases) and 83% (median of 7.5 metastases), microscopic lymphatic invasion from 0% to 3% and 35%, extrathyroid extension from 0% to 5% and 22%, and extranodal growth from 0% to 0% and 44%, whereas biochemical cure declined from 100% to 95% and 25%.Thyroid tumor diameters and basal calcitonin overlapped widely among the seven desmoplasia groups, precluding differentiation by thyroid tumor size or serum calcitonin levels.ConclusionsThyroid tumor desmoplasia, unlike serum calcitonin levels, discriminates extremely well between node‐negative and node‐positive sporadic MTC, opening new avenues for precision surgery.

Overweight as a biomarker for concomitant thyroid cancer in patients with Graves' disease.

The incidence of concomitant thyroid cancer in Graves' disease varies and Graves' disease can make the diagnosis and management of thyroid nodules more challenging. Since the majority of Graves' disease patients primarily received non-surgical treatment, identifying biomarkers for concomitant thyroid cancer in patients with Graves' disease may facilitate planning the surgery. The aim of this study is to identify the biomarkers for concurrent thyroid cancer in Graves' disease patients and evaluate the impact of being overweight on cancer risk. This retrospective cohort study analyzed 122 patients with Graves' disease who underwent thyroid surgery at Seoul St. Mary's Hospital (Seoul, Korea) from May 2010 to December 2022. Body mass index (BMI), preoperative thyroid function test, and thyroid stimulating hormone receptor antibody (TR-Ab) were measured. Overweight was defined as a BMI of 25 kg/m² or higher according to the World Health Organization (WHO). Most patients (88.5%) underwent total or near-total thyroidectomy. Multivariate analysis revealed that patients who were overweight had a higher risk of malignancy (Odds ratios, 3.108; 95% confidence intervals, 1.196-8.831; p = 0.021). Lower gland weight and lower preoperative TR-Ab were also biomarkers for malignancy in Graves' disease. Overweight patients with Graves' disease had a higher risk of thyroid cancer than non-overweight patients. A comprehensive assessment of overweight patients with Graves' disease is imperative for identifying concomitant thyroid cancer.

A Cuproptosis-Related gene Signature as a Prognostic Biomarker in Thyroid Cancer Based on Transcriptomics.

Thyroid cancer (THCA) is the most prevalent endocrinetumor, and its incidence continues to increase every year. However, the processes underlying the aggressive progression of thyroid cancer are unknown. We concentrated on the prognostic and biological importance of thyroid cancer cuproptosis-related genes in this investigation. Genomic and clinical data were obtained from the UCSC XENA website, and cuproptosis-related genes were obtained from the FerrDb website. We performed differential expression analysis and Cox regression analysis to identify possible predictive targets associated with thyroid cancer prognosis. To assess the role of CDKN2A in thyroid cancer and the ability to predict prognosis on the basis of the CDKN2A expression level, we performed immunohistochemical staining, survival analysis, immunological analysis, functional analysis, and clinical analysis with respect to CDKN2A gene expression. CDKN2A expression levels were found to be inversely correlated with thyroid cancer prognosis. Higher levels of CDKN2A expression were associated with higher T, N, and clinicopathological stage and more residual tumor cells. Through univariate and multivariate Cox regression analyses, the CDKN2A expression level was shown to be linked with thyroid cancer patients' overall survival (OS). Moreover, we discovered that CDKN2A expression was linked to a dysfunctional tumor immune microenvironment. The study shows that CDKN2A, a cuproptosis-related gene, can be used as a prognostic marker for thyroid cancer.

Prognostic Roles of Inflammatory Biomarkers in Radioiodine-Refractory Thyroid Cancer Treated with Lenvatinib.

Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers. This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers. No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039). Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.

APPLICATION OF ARTIFICIAL INTELLIGENCE IN THE DIAGNOSIS OF THYROID CANCER WITH ENHANCED COMPUTED TOMOGRAPHY

Thyroid Cancer (TC) is a common malignant tumor, head and neck in the incidence of malignant tumors in the seventh, ranked fourth in the incidence in women. There are several methods to diagnose and recognize TC, such as ultrasonic, computed tomography (CT) and other means. While, it is an important role for CT examination in the diagnosis of TC, because it has the characteristics of objectivity, repeatability, and multi-dimensional imaging, and can clearly understand the scope and spatial characteristics of the lesion. CT has unique advantages in showing lymph nodes and distant metastases, such as coarse-walled or thick-walled ring calcification. The early diagnosis of TC mainly relies on manual labor, which is very inefficient. With the continuous development of information science, the construction of TC diagnosis and recognition models based on artificial intelligence (AI) has gradually become a research hotspot. At present, research on AI-based thyroid screening models mainly focuses on four aspects: first, thyroid region segmentation and image denoising based on image-omics; second, the establishment of a high-precision TC risk prediction model based on multi-omics data; third, screening of biomarkers of TC for clinical diagnosis; fourth, establish the early screening model of TC based on AI. This paper reviews the research status of the AI-based thyroid screening model based on the above four aspects. In addition, this paper also summarizes the main challenges faced by the current AI -based TC recognition and detection model and it proposes a new research idea for the future TC early screening research based on enhanced CT.

PCDH8 is a novel prognostic biomarker in thyroid cancer and promotes cell proliferation and viability

Protocadherin 8 (PCDH8), a calcium-dependent transmembrane protein in the protocadherin family, regulates cell adhesion and signal transduction. While some studies have provided indirect evidence that PCDH8 has cancer-promoting properties, this association is controversial. In particular, its involvement in thyroid cancer (THCA) remains unclear. We aimed to elucidate the role of PCDH8 in THCA using bioinformatic analysis. Subsequently, the results were experimentally validated. The analysis conducted using the R programming language and online web tools explored PCDH8 expression levels, prognostic, and clinical implications, and its relationship with the tumor immune microenvironment in THCA. Furthermore, we examined the association between PCDH8 and co-expressed genes, highlighting their involvement in several biological processes relevant to THCA. The potential of PCDH8 as a therapeutic target for this pathology was also explored. Immunohistochemical (IHC) staining was performed on samples from 98 patients with THCA, and experimental validation was carried out. PCDH8 was significantly elevated in cancer tissues and associated with poor prognosis, several clinical factors, and immune cell and checkpoint abundance. Cox regression and survival analyses, together with Receiver Operating Curves (ROC) indicated that PCDH8 was an independent prognostic factor for THCA. Furthermore, PCDH8 impacts cell viability and proliferation, promoting tumorigenesis. Also, it influences tumor cell sensitivity to various drugs. Thus, PCDH8 might be a potential therapeutic target for THCA. IHC, cell culture, MTT, and colony formation experiments further confirmed our findings. This analysis provided insights into the potential carcinogenic role of PCDH8 in THCA, as it impacts cell viability and proliferation. Thus, PCDH8 might play an important role in its prognosis, immune infiltration, and diagnosis.

Regulatory and Interacting Partners of PDLIM7 in Thyroid Cancer.

Enigma protein, encoded by the PDLIM7 gene, is overexpressed in thyroid cancer in a stage-dependent manner, suggesting a potential involvement in the initiation and progression of thyroid cancer. The Enigma interacts with several cellular pathways, including PI3K/AKT, MDM2, and BMP-1. The Enigma is regulated by microRNAs. Specifically, we showed that the Enigma protein upregulation corresponds to the downregulation of Let-7 family genes. There is limited research on the interactions and regulation of the Enigma with other proteins/genes in thyroid cancer tissues, indicating a gap in current knowledge. Our aim is to establish the Enigma as a biomarker. We also aim to study the interacting partners of the Enigma signaling pathways and their probable miRNA regulation in thyroid cancer progression. Using Western blotting, densitometric analysis, immunoprecipitation (IP), and reverse IP, we detected the protein expression and protein-protein interactions in the corresponding papillary thyroid carcinomas (PTCs). Utilizing real-time qPCR assay and Pearson's correlation test, we highlighted the correlation between PDLIM7 and Let-7g gene expression in the same tissues. The results showed the differential upregulations of the Enigma protein in different stages of PTCs compared to benign tissues along with AKT, VDR, BMP-1, and MDM2 proteins. Loss of DBP was observed in a subset of PTCs. Strong interactions of the Enigma with PI3K/AKT and MDM2 were noted, along with a weaker BMP-1 interaction. Pearson's correlation coefficient analysis between PDLIM7 and let-7g gene expression was significant (p < 0.05); however, there was a weak inverse correlation (r = -0.27). The study suggests the potential utility of the PDLIM7-qPCR assay as a biomarker for thyroid cancer. The Enigma's interactions with key signaling pathways may provide valuable insights into the development of thyroid cancer. The study contributes to understanding the molecular mechanisms involving the Enigma protein in thyroid cancer and highlights its potential as a biomarker.

Exploration of aminopeptidase N as new biomarker for early diagnosis of thyroid cancer

False-positive diagnosis and overdiagnosis are ongoing issues in clinical diagnosis of thyroid cancer. Identifying new disease markers is crucial for early diagnosis and improved treatment. Aminopeptidase N (APN) is a promising biomarker for cancer diagnosis due to its critical roles in tumor invasion, metastasis, angiogenesis, and other processes. However, its potential as biomarker for thyroid cancer diagnosis needs further investigation. This study developed an ultra-sensitive near-infrared fluorescence probe, LAN-apn, to investigate the expression level of APN in thyroid cancer and evaluate its potential as biomarker of thyroid cancer. LAN-apn could accurately and sensitively determine APN through fluorescence method (DL = 0.069 ng/mL) and colorimetric method (DL = 4.5 ng/mL). In addition, LAN-apn allowed for successful fluorescence imaging of APN in thyroid cancer cells and thyroid cancer tumors both in vivo and in vitro, and confirmed that APN was significantly upregulated in thyroid cancer. Therefore, APN may become a new biomarker for thyroid cancer diagnosis, and LAN-apn could be used as a new imaging tool for the study of APN-thyroid cancer relationship and the early diagnosis of thyroid cancer.

The Relationship between Thyrotropin Serum Concentrations and Thyroid Carcinoma.

Thyroid Stimulating Hormone (TSH) is a hormone secreted by the pituitary gland and plays a role in regulating the production and secretion of thyroid hormones by the thyroid gland. This precise feedback loop is essential for maintaining a harmonious balance of thyroid hormones in the body, which are vital for numerous physiological processes. Consequently, TSH serves as a significant marker in assessing thyroid function, and deviations from normal TSH levels may indicate the presence of a thyroid disorder. Thyroid cancer (TC) is the malignant tumor within the endocrine system. In recent years, numerous experts have dedicated their efforts to discovering efficacious biomarkers for TC. These biomarkers aim to improve the accurate identification of tumors with a poor prognosis, as well as facilitate active monitoring of tumors with a more favorable prognosis. The role of TSH in the thyroid gland underscores its potential influence on the occurrence and progression of TC, which has garnered attention in the scientific community. However, due to the limited scope of clinical research and the dearth of high-quality foundational studies, the precise impact of TSH on TC remains unclear. Consequently, we present a comprehensive review of this subject, aiming to offer a valuable reference for future research endeavors.

Nano-approaches and Recent Advancements in Strategies to Combat Challenges Associated with Thyroid Cancer Therapies.

The prevalence of thyroid cancer (TC) is more common in women and is up to 43% in patients aged between 45-65 years. The battle against TC is hampered by the lack of effective diagnostic and therapeutic approaches. The effectiveness of surgical procedures, such as thyroidectomy and nutraceutical treatments, are accompanied by several difficulties and still require further research. Alternatively, the DNA-damaging traditional model of chemotherapy is linked to poor solubility, untoward systemic effects, and associated cytotoxicity, instituting an urgent need to establish a specialized, factual, and reliable delivery tool. In order to overcome the limitations of conventional delivery systems, nanotechnology-based delivery tools have shown the potential of articulating endless inherent implementations. The probable benefits of emerging nanotechnology-based diagnostic techniques include rapid screening and early illness diagnosis, which draws investigators to investigate and assess the possibility of this treatment for TC. Subsequently, organic (e.g., liposomes, polymer-based, and dendrimers) and inorganic (e.g., gold, carbon-based, mesoporous silica, magnetic, and quantum dots) NPs and hybrids thereof (liposome-silica, chitosan-carbon, and cell membrane-coated) have been projected for TC biomarker screening, therapy, and detection, providing better outcomes than traditional diagnostic and treatment techniques. Therefore, this review aims to offer a broad perspective on nanoplatform in TC, accompanied by present and potential future treatment options and screening techniques. The goal of cancer therapy has traditionally been to "search a thorn in a hayloft"; therefore, this article raises the possibility of treating TC using nano-oncotherapeutics, which might be useful clinically and will encourage future researchers to explore this tool's potential and drawbacks.

Liquid biopsies in thyroid cancers: a systematic review and meta-analysis.

Thyroid cancer (TC) represents the most common endocrine malignant tumor. Liquid biopsy has been suggested as a new and accurate biomarker in cancer. This systematic review analyzes the existing literature on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free DNA integrity index (cfDI), and their potential as biomarkers for TC, including the subtypes: differentiated (papillary and follicular), medullary, and anaplastic. A systematic search was performed in PubMed, Embase, and Cochrane databases for published articles in English between 1 January 1970 and 6 September 2022 (PROSPERO: CRD42022358592). The literature search generated a total of 635 articles. In total, 36 articles were included (patients = 2566). Four studies reported that higher levels of CTCs were associated with metastases and worse prognosis. Nineteen studies found the presence of mutated ctDNA in TC patients. The diagnostic accuracy in detecting BRAFV600E as ctDNA was determined in 11 studies regarding papillary TC. The pooled sensitivity, specificity, and diagnostic odds ratio were estimated at 56% (95% CI 36-74), 91% (95% CI 84-95) and 12 (95% CI 4.09-33.11), respectively. Four studies concluded that the cfDI was higher in patients with TC compared to benign thyroid lesions and healthy controls. The detection of CTCs, ctDNA, and cfDI may have a potential prognostic value in TC in relation to diagnosis, disease progression, and treatment efficacy. Despite the promising potential of CTCs, ctDNA, and cfDI in TC management, limitations hinder direct comparison and generalization of findings. Standardized methodologies, larger patient cohorts, and a consensus on relevant markers are needed to validate their clinical applicability and enhance TC management.

YTHDF3as a prognostic predictive biomarker of thyroid cancer and its correlation with immune infiltration

PurposeThyroid cancer (TC) is one of the most common endocrine malignancies, and its morbidity continues to rise. N6-methyladenosine (m6A) RNA methylation, an epigenetic modification, is an important regulator of gene expression in TC. Therefore, it’s worth finding the characteristics and predictive value of the m6A RNA methylation regulators in thyroid cancer (TC).MethodRNA-seq data of TC was downloaded from the Cancer Genome Atlas (TCGA) database to screen out the differential expressed regulators. The absolute contraction selection operator (Lasso) Cox regression was used to construct the risk model of m6A methylation regulators. The predictive value of the risk scoring model was evaluated by Kaplan Meier (K-M) analysis and receiver operating characteristic (ROC) curves. The underlying mechanism of m6A methylation regulators in TC was predicted by gene set enrichment analysis (GSEA). Further validation was performed by using immunohistochemistry (IHC) and q-PCR. The correlation between risk-related gene and immune infiltration was evaluated by Tumour Immune Estimation Resource (TIMER).ResultsIGF2BP2, YTHDF1 and YTHDF3 were screened out as strong independent prognostic factors of TC. Then a risk score model was established to further screen the predictors. Finally, according to the results of overall survival (OS) and clinical characteristics of TC, YTHDF3 was screened out as a potential predictor. Meanwhile, IHC and qPCR confirmed that YTHDF3 was expressed differential in TC. The expression of YTHDF3 was positively associated with the infiltration level of CD4+ T cells and macrophages. It was strongly correlated with a variety of immune markers in TC.ConclusionWe confirmed that YTHDF3 can be used as a potential prognostic biomarker of TC. It not only plays a decisive role in the initiation and development of TC, but also provides a new perspective for understanding the modification of m6A RNA in TC.

CTC, ctDNA, and Exosome in Thyroid Cancers: A Review.

Thyroid cancer has become more common in recent years all around the world. Many issues still need to be urgently addressed in the diagnosis, treatment, and prognosis of thyroid cancer. Liquid biopsy (mainly circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating exosomes) may provide a novel and ideal approach to solve these issues, allows us to assess the features of diseases more comprehensively, and has a function in a variety of malignancies. Recently, liquid biopsy has been shown to be critical in thyroid cancer diagnosis, treatment, and prognosis in numerous previous studies. In this review, by testing CTCs, ctDNA, and exosomes, we focus on the possible clinical role of liquid biopsy in thyroid cancer, including diagnostic and prognostic biomarkers and response to therapy. We briefly review how liquid biopsy components have progressed in thyroid cancer by consulting the existing public information. We also discuss the clinical potential of liquid biopsy in thyroid cancer and provide a reference for liquid biopsy research. Liquid biopsy has the potential to be a useful tool in the early detection, monitoring, or prediction of response to therapies and prognosis in thyroid cancer, with promising clinical applications.

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

[This retracts the article DOI: 10.1155/2022/3290479.].

Sulfur dots/Au@Ag nanorods array-based polarized ECL sensor for the detection of thyroid cancer biomarker

The combination of highly sensitive electrochemiluminescence (ECL) techniques with localized surface plasmon resonance (LSPR) effect can achieve the highly sensitive and specific detection in the analytical and biosensing applications. However, how to effectively improve the electromagnetic field intensity is an unresolved issue. Herein, we have developed an ECL biosensor based on sulfur dots and Au@Ag nanorod array architecture. Firstly, the high luminescent sulfur dots with ionic liquid capping (S dots (IL) have been prepared as the new ECL emitter. The ionic liquid greatly improved the conductivity of sulfur dots in the sensing process. Furthermore, Au@Ag nanorods array structure was constructed on the electrode surface by the evaporation induced self-assembly. On the one hand, the LSPR of Au@Ag nanorods was more significant than that of good nanomaterial due to the plasma hybridization and the competition between free electrons and oscillating electrons. On the other hand, nanorods array structure had strong electromagnetic field intensity as hot spots due to the surface plasmon coupling ECL effect (SPC-ECL) effect. Therefore, the Au @Ag nanorods array architecture not only greatly enhanced the ECL intensity of sulfur dots, but also changed the ECL signals into polarized emission. Finally, the constructed polarized ECL sensing system was used to detect the mutated BRAF DNA in the eluent of thyroid tumor tissue. The biosensor showed the linear range from 100 fM to 10 nM with a detection limit of 20 fM. The satisfactory results demonstrated that the developed sensing strategy had great potential in the clinical diagnosis of BRAF DNA mutation in thyroid cancer.

Integrated analysis of circulating and tissue proteomes reveals that fibronectin 1 is a potential biomarker in papillary thyroid cancer

Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid cancer, but 20% of cases are indeterminate (i.e., cannot be accurately diagnosed) based on preoperative cytology, which might lead to surgical removal of a normal thyroid gland. To address this concern, we performed an in-depth analysis of the serum proteomes of 26 PTC patients and 23 healthy controls using antibody microarrays and data-independent acquisition mass spectrometry (DIA-MS). We identified a total of 1091 serum proteins spanning 10–12 orders of magnitude. 166 differentially expressed proteins were identified that participate in complement activation, coagulation cascades, and platelet degranulation pathways. Furthermore, the analysis of serum proteomes before and after surgery indicated that the expression of proteins such as lactate dehydrogenase A and olfactory receptor family 52 subfamily B member 4, which participate in fibrin clot formation and extracellular matrix-receptor interaction pathways, were changed. Further analysis of the proteomes of PTC and neighboring tissues revealed integrin-mediated pathways with possible crosstalk between the tissue and circulating compartments. Among these cross-talk proteins, circulating fibronectin 1 (FN1), gelsolin (GSN) and UDP-glucose 4-epimerase (GALE) were indicated as promising biomarkers for PTC identification and validated in an independent cohort. In differentiating between patients with benign nodules or PTC, FN1 produced the best ELISA result (sensitivity = 96.89%, specificity = 91.67%). Overall, our results present proteomic landscapes of PTC before and after surgery as well as the crosstalk between tissue and the circulatory system, which is valuable to understand PTC pathology and improve PTC diagnostics in the future.

Upregulation of dendrocyte-expressed seven transmembrane protein is associated with unfavorable outcomes in differentiated thyroid cancer.

Dendritic cell infiltrates are increased in thyroid cancer but may have a defective ability to provoke effective immune responses. In this study, we aimed to identify potential thyroid cancer biomarkers linked to dendritic cell development and evaluate their prognostic relevance. Through a bioinformatics search, we identified the dendrocyte-expressed seven transmembrane protein (DCSTAMP) as a prognostic gene involved in dendritic cell differentiation for thyroid cancer. Immunohistochemical analyses of DCSTAMP expression were performed and correlated with clinical outcomes. DCSTAMP was overexpressed in a variety of types of thyroid cancers, while normal thyroid tissue or benign thyroid lesions exhibited low or undetectable DCSTAMP immunoreactivity. The results of automated quantification were consistent with subjective semiquantitative scoring. Among 144 patients with differentiated thyroid cancer, high DCSTAMP expression was associated with papillary tumor type (p < 0.001), extrathyroidal extension (p = 0.007), lymph node metastasis (p < 0.001), and BRAF V600E mutation (p = 0.029). Patients with tumors showing high DCSTAMP expression had shorter overall (p = 0.027) and recurrence-free (p = 0.042) survival. This study provides the first evidence of DCSTAMP overexpression in thyroid cancer. Apart from the prognostic implications, studies are needed to explore its potential immunomodulatory role in thyroid cancer.

Circulating microRNA as potential diagnostic and prognostic biomarkers of well-differentiated thyroid cancer: A review article.

Half of all people aged 50 and over develop a thyroid nodule in their lifetime, exclusion of cancer is required in each case. Nodule tissue sampling is performed by way of fine needle aspiration biopsy (FNAB), however a definite diagnosis is possible only in 30% of cases. The discovery of a diagnostic biomarker to discriminate between thyroid cancer and benign nodules would therefore greatly improve current clinical practice. Using the databases of Medline, Embase and Pubmed we identified 21 original research papers examining various microRNA as potential biomarkers. Currently, the most evidence supporting diagnostic utility exists for miRNA-222. It has been shown repeatedly to have potential in diagnosis of PTC & MTC as well as being linked with the most prognostic factors of all microRNA. To a lesser extent, evidence seems to support the diagnostic and prognostic utility of miR-146b, Let-7 family, miR-221 for PTC and miR-21 for PTC & FTC. MicroRNA appear to show promise as potential diagnostic and prognostic biomarkers, however there is still not enough data to produce a consensus. Continued research should be undertaken with streamlined protocols.

Highly sensitive detection of thyroglobulin based on sandwich-type electrochemical immunoassay.

As a dimeric protein, thyroglobulin (Tg) is an important biomarker for different thyroid cancer (DTC), so designing effective method to detect Tg is of great significance. In this work, by preparing β-cyclodextrin (CD) functionalized carbon nanotubes (CNTs) nanohybrid (CD-CNTs) as carrier to immobilize primary antibody (Ab1) of Tg, assembling sulfydryl ferrocene (Fc) and secondary antibody (Ab2) on the surface of nanogold (Au) as signaling amplifier (Ab2-Au-Fc), a simple and sensitive sandwich-type electrochemical immunoassay (STEM) of Tg was designed herein for the first time. In brief, CNTs show large surface area and conductivity, while CD offers superior host-guest recognition capability that can bound with Ab1; meanwhile, Fc probe can offer stable electrochemical signal that is proportionable to the concentration of Tg. Under the optimum conditions, the proposed STEM platform shows excellent sensing results for Tg detection: a considerable low analytical detection (0.5ngmL-1) and wide linearity (2 to 200ngmL-1), suggesting the designed STEM platform offers potential real applications for detect Tg.

EDB-FN targeted probes for the surgical navigation, radionuclide imaging, and therapy of thyroid cancer.

Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [18F]-NOTA-PEG4-EDBp([18F]-EDBp), and [177Lu]-DOTA-PEG4-EDBp ([177Lu]-EDBp), for the surgical navigation, radionuclide imaging, and therapy of TC. Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging, and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients. The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1-h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8.00 d vs. 8.00 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety. Cy5-EDBp, [18F]-EDBp, and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging, and radionuclide therapy of TC, respectively.