Diagnosis Of Papillary Thyroid Cancer Research Articles

Spatial and Single-Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer.

Recurrence and metastasis are the major issues for papillary thyroid cancer (PTC). Current morphological and molecular classification systems are not satisfied for PTC diagnosis due to lacking variant-specific morphological criteria and high signal-to-noise in mutation-based diagnosis, respectively. Importantly, intratumor heterogeneity is largely lost in current molecular classification system, which can be resolved by single cell RNA sequencing (scRNA-seq). However, scRNA-seq loses spatial information and morphological features. Herein, scRNA-seq is integrated and spatially-resolved transcriptomics (SRT) to elaborate the mechanisms underlying the spatial heterogeneity, malignancy and metastasis of PTCs by associating transcriptome and local morphology. This results demonstrated that PTC cells evolved with multiple routes, driven by the enhanced aerobic metabolism and the suppressed mRNA translation and protein synthesis and the involvement of cell-cell interaction. Two curated malignant and metastatic footprints can discriminate PTC cells from normal thyrocytes. Ferroptosis resistance contributed to PTC evolution. This results will advance the knowledge of intratumor spatial heterogeneity and evolution of PTCs at spatial and single-cell levels, and propose better diagnostic strategy.

Experience of applying convolutional neural network for binary classifcation of microphotographs of thyroid cytology specimens

Objective: to evaluate the effectiveness of a convolutional neural network model for automated cytologic diagnosis of papillary thyroid cancer and benign thyroid nodules.Material and Methods. The convolutional neural network was developed in the Python programming language using the TensorFlow 2.15.0 open source library. For the study, a dataset that included two categories of pathologies was generated: 1597 microphotographs of papillary carcinoma and 767 microphotographs of benign nodules (colloid goiter and adenomatous nodules). To form a training sample and evaluate the model’s performance metrics on the test sample, the dataset was divided in a ratio of 80/20.Results. In classifying papillary carcinoma, the model achieved precision of 89.3 %, recall of 92.4 %, specifcity of 77.4 % and F1 score of 91.4 %. When identifying benign nodules, the presicion, recall, specifcity and F1 score were 83.3 %, 77.4 %, 92.4 %, and 80.3 %, respectively, indicating a higher rate of false-positive and false-negative predictions. The AUC was 0.91 at the individual microphotograph level and 0.94 at the serial microphotograph level from one patient, indicating the high ability of the trained model to differentiate between malignant and benign thyroid lesions based on microphotographs of fne-needle aspiration biopsy specimens.Conclusion. Further improvement of the neural network model by training on larger and more diverse datasets of microphotographs of cytological specimens of the thyroid gland will help improve its diagnostic range and performance. The developed model can be used to develop software for identifying thyroid pathologies.

A Comparative Study on BRAFV600E Mutation, Sonographic Findings, and Pathologic Characteristics in Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) and Invasive Follicular Variant of Papillary Thyroid Carcinoma (IFVPTC)

Objective: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) comprise a new subgroup of thyroid tumors of follicular origin with borderline histologic features that lack evidence of either capsular or vascular invasion. In contrast to the invasive follicular variant of papillary thyroid carcinoma (IFVPTC), adverse events such as cancer-related death, distant or regional metastases, and structural or biochemical recurrence do not occur in patients with NIFTP. Many studies have been done to elucidate these two specific types of papillary thyroid cancer (PTC) and reduce aggressive therapeutic actions. This study compares molecular, cytological, and radiologic features of NIFTP and IFVPTC. Materials and Methods: Two groups of patients with NIFTP and IFVPTC (n = 18 in each group) who were referred to the endocrine clinic, at Imam Reza Hospital, were enrolled in this crosssectional study. Molecular analysis for BRAFV600E mutation of thyroid tissue was evaluated for all cases. Patient data included: age, sex, type of surgery, thyroid sonographic findings, and prior cytological diagnosis with the Bethesda system for reporting thyroid cytopathology. Results: Only two cases in the IFVPTC group were positive for BRAFV600E mutation. The majority of NIFTP cases were diagnosed as benign lesions (8/18). In contrast, the majority of IFVPTC cases were diagnosed as suspicious for malignancy on cytology (7/18). The mean nodule size in ultrasound in the NIFTP group (41.81 ± 20.43 mm) was larger than the IFVPTC group (36.72 ± 20.73 mm) (p =0.47). Most cases in the IFVPTC group had significantly multiple nodules (72.2%), while most cases in the NIFTP group (81.3%) had solitary nodules. Nodule composition in both groups was solid and complex; however, no cystic nodules were detected in ultrasound examinations. Furthermore, no calcification or lymphadenopathy was seen in the majority of cases in ultrasound. In the IFVPTC group, 47.1% and 35.3% of nodules were hyperechoic and hypoechoic, respectively, while 23.1%, 38.5%, and 23.1% of nodules in the NIFTP group were heterogenic, hyperechoic, and hypoechoic, respectively. Conclusion: According to our findings, only 11.1% of IFVPTC cases were BRAFV600E-positive, while none of the patients in the NIFTP group showed this mutation. However, IFVPTC was predominantly associated with a preceding diagnosis of PTC on FNA, and NIFTP was associated with the preceding diagnosis of benign lesions and follicular neoplasm. Sonographic findings failed to distinguish NIFTP from IFVPTC.

7744 Diagnosis of Papillary Thyroid Cancer After Radiofrequency Ablation

7744 Diagnosis of Papillary Thyroid Cancer After Radiofrequency Ablation

Development and Verification of Diagnosis Model for Papillary Thyroid Cancer Based on Pyroptosis-Related Genes: A Bioinformatic and in vitro Investigation.

The incidence of papillary thyroid cancer (PTC) has been increasing annually; however, early diagnosis can improve patient outcomes. Pyroptosis is a programmed cell death modality that has received considerable attention recently. However, no studies have reported using pyroptosis-related genes in PTC diagnosis. Analyzed 33 pyroptosis-related genes in PTC transcriptome data from the Gene Expression Omnibus database. Subsequently, used the Least Absolute Shrinkage and Selection Operator (LASSO) model to construct a PTC molecular diagnostic model. Furthermore, confirmed differences in the expression of five genes between PTC and non-tumor tissues using immunohistochemistry. Collected 338 PTC and control samples to construct a five-gene PTC diagnostic model, which was then validated using a training set and underwent correlation analysis with immune cell infiltration. Additionally, validated the biological functions of the core gene NOD1 in vitro. The five-gene PTC diagnostic model demonstrated good diagnostic value for PTC. Moreover, identified three reliable subtypes of pyroptosis and found that NOD1 is involved in tumor-suppressive microenvironment formation. Notably, patients with high NOD1 expression had lower Progression-Free Survival (PFS). Additionally, NOD1 expression was positively correlated with immune markers such as CD47, CD68, CD3, and CD8. Lastly, inhibiting NOD1 showed significant anti-PTC activity in vitro. Our results suggest that pyroptosis-related genes can be used for PTC diagnosis, and NOD1 could be a promising therapeutic target.

Elevated Cancer-Associated Hyaluronan Correlates With Diagnosis and Lymph Node Metastasis of Papillary Thyroid Cancer

The glycosaminoglycan hyaluronan (HA) plays an important role in tumor progression. However, its biological and clinical significance in papillary thyroid cancer (PTC) remains unknown. Immunohistochemistry was performed to examine HA expression in tissues from PTC patients. Two PTC cell lines were treated with HA synthesized inhibitor against HA production to assess its function. Serum HA levels from 107 PTC patients, 30 Hashimoto thyroiditis patients, and 45 normal controls (NC) were measured by chemiluminescence immunoassay. HA levels in fine needle aspiration (FNA) washouts obtained from thyroid nodules and lymph nodes (LNs) were measured by chemiluminescence immunoassay. Area under the curve (AUC) was computed to evaluate HA’s clinical value. HA was highly expressed in PTC. Reducing HA production significantly inhibited PTC cell proliferation and invasion. Importantly, serum HA levels in PTC were significantly higher than those in NCs and Hashimoto thyroiditis and allowed distinguishing of thyroid cancers from NCs with high accuracy (AUC = 0.782). Moreover, elevated serum HA levels in PTC correlate with LN metastasis. HA levels in FNA washouts from PTC patients were significantly higher than those in benign controls, with a high AUC value (0.8644) for distinguishing PTC from benign controls. Furthermore, HA levels in FNA washouts from metastatic LN were significantly higher than those in nonmetastatic LN, with a high AUC value (0.8007) for distinguishing metastatic LNs from nonmetastatic LNs. HA levels in serum and FNA washout exhibited a potential significance for PTC diagnosis and an indicator for LN metastasis in patients with PTC.

Hsa_circ_0010023 promotes the development of papillary thyroid carcinoma by sponging miR-1250-5p.

Papillary thyroid cancer (PTC) is the most common thyroid tumor (TC). However, there is still a lack of effective indicators for PTC detection and prognosis. We intended to find a novel tumor marker for the progression of PTC. The expression of circRNAs was measured by quantitative real-time polymerase chain reaction (qRT-PCR). SiRNA transfection was used to knockdown the expression of hsa_circ_0010023 in K1 cells. Cell proliferation was evaluated using cell counting and CCK8. Cell apoptosis was analyzed using flow cytometry. Hsa_circ_0010023 downstream pathways were predicted with bio-informatics analysis. The miR-1250-5p and MAPK1 were measured by qRT-PCR. The interaction between miR-1250-5p and hsa_circ_0010023 was vertified by dual-luciferase reporter assay. Among the four circRNAs screened, only hsa_circ_0010023 and hsa_circ_0128482 were highly expressed in PTC (P < 0.05). The expression of hsa_circ_0010023 was significantly correlated with lymph node metastasis and extrathyroid infiltration (P < 0.05). Compared with the control group, the cell proliferation of the si-circ-0010023 group was significantly inhibited (P < 0.05). Knockdown of hsa_circ_0010023 promotes apoptosis of K1 cells (P < 0.001). The expression of hsa_circ_0010023 was negatively correlated with miR-1250-5p and positively correlated with MAPK1. MiR-1250-5p overexpression significantly reduced the luciferase activity of wild type plasmid (hsa_circ_0010023 WT), but not that of mutant type plasmid (hsa_circ_0010023 MUT). The expression level of hsa_circ_0010023 was positive related to the progression of PTC, and hsa_circ_0010023 may promote PTC through sponging miR-1250-5p. Hsa_circ_0010023 may be a potential bio-marker for the diagnosis of PTC.

Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics.

Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.

Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Abstract LB276: qPCR in the diagnosis of papillary thyroid cancer: Assessment of BRAF V600E mutation in FNA biopsies of thyroid nodules

Abstract Papillary thyroid carcinoma (PTC) accounts for up to 90% of thyroid cancer cases, and its differentiation from benign conditions presents a challenge in clinical practice. Fine needle aspiration biopsy (FNAB) has become a recommended practice for evaluating thyroid nodules (TN) with imaging features suspicious of malignancy. Although FNAB demonstrates high accuracy in discriminating TN, a significant number are classified as malignant indeterminate (MTI), which can only be fully diagnosed by post-surgical histologic evaluation. Up to 30% of FNAB findings are expected to be MTI, leading to a high rate of unnecessary hemithyroidectomies in about 75% of patients. In PTC, the most common mutation is c.T1799A in the BRAF gene (rs113488022), resulting in V600E in the B-raf protein, leading to an increase expression by altering the MAPK pathway. The aim of this study was to evaluate the efficacy of discriminating patients with malignant and benign TNs by detecting BRAF V600E in tissue from FNAB for molecular diagnosis of PTC. The qPCR technique with allele-specific probes was used to detect the BRAF c.1799T&amp;gt;A mutation in somatic DNA samples extracted by FNAB from TN (n=99) with suspected malignancy by ultrasonography. Cytologic diagnosis of biopsies was performed using the Bethesda System (TBSRTC). Diagnostic accuracy measures for evaluation of BRAF c.1799T&amp;gt;A as a diagnostic tool were performed with MedCalc software. Of the 99 patients, it was determined by cytology that 50 patients (50.51%) had PTC and 49 benign neoplasms (49.49%). The mutation was detected in 28 of the PTC samples (56%) (AA homozygotes [n=12, 24%] and AT heterozygotes [n=16, 32%). No mutation carriers were found among patients with benign neoplasms. Regarding accuracy measures were 56% for sensitivity of 56% and 100% specificity. The positive predictive value was 100% and the negative predictive value was 69.01%, with an accuracy of 77.78%. Finally, the negative likelihood ratio (LR-) value was 0.44 (95% CI: 0.32 to 0.60), while the positive likelihood ratio (LR+) value could not be calculated as there were no patients with the mutation in the group of patients with benign TN. In conclusion, our results suggest that the presence of BRAF c.1799T&amp;gt;A mutation could be indicative of PTC, confirming its usefulness in the differentiation between malignant and benign tumors. BRAF V600E detection may be valuable as an adjunct to conventional cytology, improving diagnostic accuracy and reducing the need for unnecessary surgical procedures. While highlighting the potential utility of this technique as a diagnostic tool, further analysis and consideration of other metrics is recommended for a full evaluation of its clinical relevance. Citation Format: Anette R. Gastelum-Quiroz, Andrea Ross-Orozco, Marco A. Álvarez-Arrazola, Eliakym Arambula-Meraz, Karla L. Morales-Hernández, Hanna M. Tolosa-Lerma, Fred Luque-Ortega, Paola Y. Sánchez-Aboytes, Noemí García-Magallanes. qPCR in the diagnosis of papillary thyroid cancer: Assessment of BRAF V600E mutation in FNA biopsies of thyroid nodules [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB276.

Neurotrophic-tyrosine receptor kinase gene fusion in papillary thyroid cancer: A clinicogenomic biobank and record linkage study from Finland.

Selective tropomyosin receptor kinase (TRK) inhibitors are approved targeted therapies for patients with solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Country-specific estimates of NTRK gene fusion frequency, and knowledge on the characteristics of affected patients, are limited. We identified patients with histologically-confirmed papillary thyroid cancer (PTC) from Finland's Auria Biobank. TRK protein expression was determined by pan-TRK immunohistochemistry. Immuno-stained tumor samples were scored by a certified pathologist. Gene fusions and other co-occurring gene alterations were identified by next generation sequencing. Patient characteristics and vital status were determined from linked hospital electronic health records (EHRs). Patients were followed from 1 year before PTC diagnosis until death. 6/389 (1.5%) PTC patients had an NTRK gene fusion (all NTRK3); mean age 43.8 years (and none had comorbidities) at PTC diagnosis. Gene fusion partners were EML4 (n = 3), ETV6 (n = 2), and RBPMS (n = 1). Of 3/6 patients with complete EHRs, all received radioactive iodine ablation only and were alive at end of follow-up (median observation, 9.12 years). In conclusion, NTRK gene fusion is infrequent in patients with PTC. Linkage of biobank samples to EHRs is feasible in describing the characteristics and outcomes of patients with PTC and potentially other cancer types.

Clinical and morphological features and unsolved issues in diagnosis of aggressive forms of papillary thyroid carcinoma

Differentiated thyroid cancer (DTC) is a disease with a favorable clinical course and high survival rate compared to other epithelial tumors. The majority of DTC (up to 85 %) is represented by various subtypes of papillary thyroid cancer (PTC). Aggressive forms of PTC characterized by early lymphogenous and hematogenous metastasis, low avidity to radioiodine therapy (RIT), low relapse-free survival rates and high mortality rate compared to other types of PTC occur among them. Preoperative diagnosis of PTC is based on the results of ultrasound (US) examination and fine-needle aspiration biopsy (FNA) with cytological examination of the aspirate. At the same time, the capabilities of cytological examination in determining the histological type of PTC are limited and it does not allow to predict its aggressiveness and plan adequate treatment. Molecular genetic tests of the tumor cytological and morphological material are effective in prognosis of aggressiveness of PTC due to the determination of specific mutations in the BRAF, TERT, RAS genes and the quantitative expression of oncogenic and tumor suppressive microRNAs. Some of these indicators are already used in the morphological classification of tumors of the endocrine system. At the same time, there are contradictory data concerning the connection of the molecular genetic portrait of PTC, the clinical manifestations of its aggressiveness (extrathyroidal invasion, early metastasis, and radioiodine resistance) and its pathomorphological structure. We tried to summarize and analyze the literature data regarding the diagnosis of aggressive variants of PTC.

The emerging role and clinical significance of circRNAs in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common type of thyroid malignancy, and its global incidence has been gradually increasing. For advanced PTC, the mortality rates are also increasing yearly. Despite advancements in diagnosis and treatment, some advanced PTC exhibit aggressive behaviors, leading to a poor prognosis. CircRNAs are a class of non-coding RNAs characterized by a covalently closed loop structure. Their stability and abundance have positioned them as promising diagnostic and prognostic biomarkers. Numerous studies have identified dysregulated circRNAs in PTC tissues and cell lines, suggesting their involvement in PTC initiation and progression. In this review, we provide an overview of circRNAs and systematically discuss their role in PTC. CircRNAs affect cancer progression by regulating the Wnt/β-catenin, PI3K/AKT, MAPK pathways, and others. Furthermore, circRNAs have been implicated in PTC metastasis and chemoresistance. We highlight their potential value as diagnostic markers, therapeutic targets, and prognostic indicators. In conclusion, circRNAs play a critical role in PTC, and dysregulated circRNAs influence multiple signaling pathways and cellular processes involved in tumorigenesis and metastasis. It represents a promising avenue for advancing the diagnosis, management, and treatment of PTC.

SAT536 A Case of Papillary Thyroid Cancer in Multiple Cervical Lymph Nodes, But Not Found in Thyroid Tissue on Pathology

Abstract Disclosure: M.A. Green: None. G.Y. Kim: None. Introduction:As technology advances, imaging becomes increasingly frequent and within the thyroid gland nodules can often be detected. After detection comes evaluation and lymph nodes within the neck are an integral part of this step. For that reason, fine needle aspiration (FNA) of cervical lymph nodes is known to lend a hand toward diagnosis. Here we present a patient who was diagnosed with Papillary Thyroid Cancer (PTC) from FNA pathology of a lymph node, but PTC was not noted within pathology of the thyroid tissue after total thyroidectomy. Case Presentation: This patient is a 34 year-old female with a history of ovarian cancer who presented to the clinic for a thyroid nodule and Hashimoto’s disease. A bed side ultrasound noted a right upper pole 1.6 x 0.6 x 0.6 cm thyroid nodule and a solid 1.8 x 1.5 x 0.8 cm nodule superior to the isthmus likely representing a delphian lymph node. As well, significant cervical lymphadenopathy was seen. A biopsy of the right upper pole nodule was nondiagnostic on FNA, but the delphian lymph node superior to the isthmus was positive for PTC. The patient then underwent total thyroidectomy and right and central neck lymph node dissections. Interestingly, PTC was noted in 3 of 27 lymph nodes in the central compartment, 5 of 18 lymph nodes excised with the thyroid tissue with extranodal extension, and 5 of 24 lymph nodes in the right neck compartment, but not noted in the thyroid tissue itself. The largest metastatic dimension of PTC within the cervical lymph nodes was noted to be 3 cm. The pathology noted a 1.0 cm tumor in the right lobe “approaching skeletal muscle” and psammoma bodies within the left lobe. After the patient’s surgery her stimulated thyroglobulin reported as 0.21 NG/mL and thyroglobulin antibody 2 IU/mL. She was then able to receive 30 mCi of I 131 sodium iodide. TSH maintained at goal on levothyroxine 200 mcg daily. Discussion: Diagnosis of PTC within multiple cervical lymph nodes, but not noted on thyroid pathology is very uncommon. It is highly unlikely in our patient that a cancer within the thyroid does not exist and there are theories to postulate this unique finding. These include missed pathology on the dissection, tumor regression prior to removal, or possibly ectopic tissue as the source of PTC. Although in our patient, given the significant amount of positive cervical lymph nodes, it is hard to believe that ectopic tissue away from the neck was the source or that tumor regression occurred. The pathological findings of psammoma bodies suggest the presence of PTC that spread to the lymphatic system. As well, the nature of thyroid removal leads to some destruction of tissue prior to evaluation. This case highlights the importance of thorough lymph node evaluation as a complete part of preoperative PTC assessment. Presentation Date: Saturday, June 17, 2023

Integrated analysis of tumor microenvironment features to establish a diagnostic model for papillary thyroid cancer using bulk and single-cell RNA sequencing technology

BackgroundCharacterizing tumor microenvironment using single-cell RNA sequencing has been a promising strategy for cancer diagnosis and treatment. However, a few studies have focused on diagnosing papillary thyroid cancer (PTC) through this technology. Therefore, our study explored tumor microenvironment (TME) features and identified potential biomarkers to establish a diagnostic model for papillary thyroid cancer.MethodsThe cell types were identified using the markers from the CellMarker database and published research. The CellChat package was conducted to analyze the cell–cell interaction. The SCEVAN package was used to identify malignant thyroid cells. The SCP package was used to perform multiple single-cell downstream analyses, such as GSEA analysis, enrichment analysis, pseudotime trajectory analysis, and differential expression analysis. The diagnostic model of PTC was estimated using the calibration curves, receiver operating characteristic curves, and decision curve analysis. RT-qPCR was performed to validate the expression of candidate genes in human papillary thyroid samples.ResultsEight cell types were identified in the scRNA-seq dataset by published cell markers. Extensive cell–cell interactions like FN1/ITGB1 existed in PTC tissues. We identified 26 critical genes related to PTC progression. Further, eight subgroups of PTC tumor cells were identified and exhibited high heterogeneity. The MDK/LRP1, MDK/ALK, GAS6/MERTK, and GAS6/AXL were identified as potential ligand-receptor pairs involved in the interactions between fibroblasts/endothelial cells and tumor cells. Eventually, the diagnostic model constructed by TRPC5, TENM1, NELL2, DMD, SLC35F3, and AUTS2 showed a good efficiency for distinguishing the PTC and normal tissues.ConclusionsOur study comprehensively characterized the tumor microenvironment in papillary thyroid cancer. Through combined analysis with bulk RNA-seq, six potential diagnostic biomarkers were identified and validated. The diagnostic model we constructed was a promising tool for PTC diagnosis. Our findings provide new insights into the heterogeneity of thyroid cancer and the theoretical basis for diagnosing thyroid cancer.

Bioinformatics analysis of the prognostic and clinical value of senescence-related gene signature in papillary thyroid cancer.

Cellular senescence can both inhibit and promote the occurrence of tumors, so how to apply cellular senescence therapy is of great importance. However, it is worth to be analyzed from multiple perspectives by researchers, especially for tumors with a high incidence like papillary thyroid cancer (PTC). We obtained senescence-related differentially expressed genes (SRGs) from The Cancer Genome Atlas (TCGA) and gene expression omnibus database. Enrichment analysis of SRGs was performed via gene ontology and Kyoto Encyclopedia of Genes and Genomes. Prognostic model was constructed by univariate and multivariate Cox regression analysis. Evaluation of clinical value was analyzed via Receiver operating characteristic curve, Kaplan-Meier curve and Cox regression. Immune infiltrates were investigated through ESTIMATE and single-sample gene set enrichment analysis. Immunohistochemical images were obtained from The Human Protein Atlas. Twenty-seven SRGs from TCGA cohort and gene expression omnibus datasets were found. These genes are mainly concentrated in senescence-related terms and pathways, including "DNA damage response, signal transduction by p53 class mediator," "signal transduction in response to DNA damage," "p53 signaling pathway" and "Endocrine resistance." Based on SRGs, prognostic model was constructed by E2F transcription factor 1, snail family transcriptional repressor 1 and phospholipase A2 receptor 1. PTC patients were divided into a low-risk group and a high-risk group according to the median value (cutoff point = 0.969) of risk score in TCGA cohort. The diagnostic efficiency of this model is good (area under curve = 0.803, 0.809, and 0.877 at 1, 2, and 3 years in TCGA; area under curve = 0.964, 0.813 in GPL570 and GPL96), particularly advanced grade, state and tumor mutation burden, such as Stage III - IV, T3 - 4, H-tumor mutation burden. Furthermore, High-risk group was significantly associated with poor prognosis and more immune infiltration. Our prognostic model has a good diagnostic and prognostic efficacy, and there is a certain clinical application value. In addition, we provide the first new insight into the genesis, diagnosis, prognosis and treatment of PTC based on senescence-related genes.

Overall survival trends of papillary thyroid cancer: A Surveillance, Epidemiology, and End Results (SEER) population-based data (2002-2016).

e18108 Background: In the United States, the 5-year survival rate for patients with thyroid cancer is 98%. However, survival rates are mainly influenced by the type of thyroid cancer and the stage of the disease. The tremendous research in the area and the need to assess outcomes of recently implemented treatments necessitate the evaluation of the epidemiology and overall survival rates of the most common type of this malignancy, papillary thyroid cancer (PTC). Although the cause-specific survival (CSS) of Papillary Thyroid Cancer (PTC) patients has been extensively investigated, the overall survival (OS) of these patients is unclear. In this study, we aim to conduct an evaluation of survival trends after PTC diagnosis by stage of disease for the years 2002 through 2016 in the United States. Methods: We used the SEER 9 database to study PTC cases during 2002-2016. The patient survival data for the three disease stages (local, regional, and distal) were compared for the two time periods of interest, (2002-2008) and (2009-2016). The data for each cohort were split into six groups, (those whose deaths were in each of the five one-year intervals and those surviving the five-year follow-up period). These categorical counts were compared by the chi-square test of contingency table data. Statistical significance was taken as a p-value less than 0.05. Results: We reviewed 73,333 PTC cases in the United States from 2002 through 2016. There was an overall survival improvement with the exception of the distal stage, which did not demonstrate any statistical difference in the 2-time frames of interest. For local sites, there was a highly significant difference between the survival distributions of patients in the two time periods of interest (p = 0.0095; chi-square test statistic = 15.20 with 5 degrees of freedom). For regional sites, there was a highly significant difference between the survival distributions of patients in the two time periods of interest (p = 0.0077; chi-square test statistic = 15.72 with 5 degrees of freedom). For the distant stage, there was no significant difference between the survival distributions of patients in the two time periods of interest (p = 0.28; chi-square test statistic = 6.25 with 5 degrees of freedom). Conclusions: PTC’s survival rates have shown an improvement over the years 2002 through 2016, mostly noted in the local and regional stages. Although most patients with PTC have a favorable prognosis when conventional treatments are implemented, local recurrence and distant metastasis of advanced PTCs still hamper the survival and clinical management in certain patients.

Integrated metabolic and genetic analysis reveals distinct features of human differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) affects thousands of lives worldwide each year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis. Unfortunately, thyroidectomy and/or radioiodine therapy often worsen(s) quality of life and might be unnecessary in indolent DTC cases. On the other hand, the lack of biomarkers indicating a potential metastatic thyroid cancer imposes an additional challenge to managing and treating patients with this disease. The presented clinical setting highlights the unmet need for a precise molecular diagnosis of DTC and potential metastatic disease, which should dictate appropriate therapy. In this article, we present a differential multi-omics model approach, including metabolomics, genomics, and bioinformatic models, to distinguish normal glands from thyroid tumours. Additionally, we are proposing biomarkers that could indicate potential metastatic diseases in papillary thyroid cancer (PTC), a sub-class of DTC. Normal and tumour thyroid tissue from DTC patients had a distinct yet well-defined metabolic profile with high levels of anabolic metabolites and/or other metabolites associated with the energy maintenance of tumour cells. The consistency of the DTC metabolic profile allowed us to build a bioinformatic classification model capable of clearly distinguishing normal from tumor thyroid tissues, which might help diagnose thyroid cancer. Moreover, based on PTC patient samples, our data suggest that elevated nuclear and mitochondrial DNA mutational burden, intra-tumour heterogeneity, shortened telomere length, and altered metabolic profile reflect the potential for metastatic disease. Altogether, this work indicates that a differential and integrated multi-omics approach might improve DTC management, perhaps preventing unnecessary thyroid gland removal and/or radioiodine therapy. Well-designed, prospective translational clinical trials will ultimately show the value of this integrated multi-omics approach and early diagnosis of DTC and potential metastatic PTC.

FREQUENCY OF HASHIMOTO THYROIDITIS IN PAPILLARY THYROID CANCER PATIENTS AND ITS IMPACT ON THEIR OUTCOME

Introduction: There is conicting information on Hashimoto thyroiditis (HT) and the risk of cancer. The purpose of this study was to look at the coexistence of papillary thyroid carcinoma (PTC) and HT. Aims: To aims of the study hashimoto thyroiditis in patients with papillary thyroid cancer: frequency and effect on their outcome. Material and methods: It is a retrospective review of patients who got admitted with the diagnosis of papillary thyroid cancer from Jan 2021 to December 2022 at MGIMS Sewagram, Maharashtra. Results: In the entire presently analyzed material, the presence of central compartment lymph node metastases was signicantly higher in patients with cancer and Hashimoto thyroiditis (PTC- HT081 (30.4 %) vs. non-HT-PTC0121 (12.8 %)). According to numerous reports, metastatic foci in cervical lymph nodes accompany both “clear” cancer forms and tumors presenting with symptoms of chronic lymphocytic thyroiditis. Conclusion: Analyzing this aspect, we may say that primary total thyroidectomy also limits the number of permanent complications, which in a signicant percentage of cases pose a considerable threat in the course of reoperation. In our opinion, the above-described rationale provides a foundation for considering radical surgical treatment in cases of nodular lesions being present in immunologically altered thyroid gland

The role of DAP IV activity testing in the cytological examination of tumors of the «gray zone» TBSRTC IV in the prediction of papillary thyroid cancer and metastases

One of the most effective methods of thyroid nodules diagnosis is the fine‑needle aspiration puncture biopsy (FNAPB), allowing evaluation of the cytological characteristics of thyroid tumors. To improve the diagnostic efficiency of cytological investigations, additional methods can be implemented, including cytochemical determination of dipeptidyl aminopeptidase (DAP IV).&#x0D; Objective — to analyze and establish the DAP IV activity thresholds, at which the probability of detecting papillary thyroid cancer (PTC) and its metastases in lymph nodes is clinically significant in patients with cytological conclusion of the TBSRTC IV category.&#x0D; Materials and methods. For the first time in Ukraine, an analysis was made of the possibility of using DAP IV to predict papillary cancer and its metastases in cases of tumors with TBSRTC IV using ROC analysis to determine the threshold values of DAP IV activity, defining the clinically significant probability of metastases.&#x0D; Results. It has been established that 6 is the cut‑off DAP IV value for diagnosis of papillary thyroid cancer, and 8 is the cut‑off point for the presence of its metastatic deposits. Thus, in case of DAP IV activity values between 6 and 8, the probability of papillary thyroid cancer diagnosis and its metastases significantly increases. The prognostic value of a positive result, i.e. obtaining a malignant diagnosis with DAP IV 6 activity, is 85.1%, which can be interpreted as high. With increasing DAP IV activity in patients with TBSRTC IV category, the probability of the reveal of papillary thyroid cancer metastases increases (threshold value of activity for DAP IV metastases 8 with counter sensitivity 0.267).&#x0D; Conclusions. The obtained results allow a practitioner to choose treatment options: with values of DAP IV &lt;6, the alternative therapies or active monitoring can be used, and with DAP IV &lt;8, the need for preventive dissection may not be advisory.