Diagnosis Of Papillary Thyroid Cancer Research Articles

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>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>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>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.

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. Methods & Materials: 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 cross-sectional 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.

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).
 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.
 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.
 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).
 Conclusions. The obtained results allow a practitioner to choose treatment options: with values of DAP IV <6, the alternative therapies or active monitoring can be used, and with DAP IV <8, the need for preventive dissection may not be advisory.

Identification of potential LncRNAs as papillary thyroid carcinoma biomarkers based on integrated bioinformatics analysis using TCGA and RNA sequencing data

The roles and mechanisms of long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remain elusive. We obtained RNA sequencing (RNA-seq) data of surgical PTC specimens from patients with thyroid cancer (THCA; n = 20) and identified differentially expressed genes (DEGs) between cancer and cancer-adjacent tissue samples. We identified 2309 DEGs (1372 significantly upregulated and 937 significantly downregulated). We performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment, and protein–protein interaction network analyses and screened for hub lncRNAs. Using the same methods, we analyzed the RNA-seq data from THCA dataset in The Cancer Genome Atlas (TCGA) database to identify differentially expressed lncRNAs. We identified 15 key differentially expressed lncRNAs and pathways that were closely related to PTC. Subsequently, by intersecting the differentially expressed lncRNAs with hub lncRNAs, we identified LINC02407 as the key lncRNA. Assessment of the associated clinical characteristics and prognostic correlations revealed a close correlation between LINC02407 expression and N stage of patients. Furthermore, receiver operating characteristic curve analysis showed that LINC02407 could better distinguish between cancerous and cancer-adjacent tissues in THCA patients. In conclusion, our findings suggest that LINC02407 is a potential biomarker for PTC diagnosis and the prediction of lymph node metastasis.

A new molecular subclassification and in silico predictions for diagnosis and prognosis of papillary thyroid cancer by alternative splicing profile.

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. However, different PTC variants reveal high heterogeneity at histological, cytological, molecular and clinicopathological levels, which complicates the precise diagnosis and management of PTC. Alternative splicing (AS) has been reported to be potential cancer biomarkers and therapeutic targets. Method: Here, we aim to find a more sophisticated molecular subclassification and characterization for PTC by integrating AS profiling. Based on six differentially expressed alternative splicing (DEAS) events, a new molecular subclassification was proposed to reclassify PTC into three new groups named as Cluster0, Cluster1 and Cluster2 respectively. Results: An in silico prediction was performed for accurate recognition of new groups with the average accuracy of 91.2%. Moreover, series of analyses were implemented to explore the differences of clinicopathology, molecular and immune characteristics across them. It suggests that there are remarkable differences among them, but Cluster2 was characterized by poor prognosis, higher immune heterogeneity and more sensitive to anti-PD1 therapy. The splicing correlation networks proved the complicated regulation relationships between AS events and splicing factors (SFs). An independent prognostic indicator for PTC overall survival (OS) was established. Finally, three compounds (orantinib, tyrphostin-AG-1295 and AG-370) were discovered to be the potential therapeutic agents. Discussion: Overall, the six DEAS events are not only potential biomarkers for precise diagnosis of PTC, but also the probable prognostic predictors. This research would be expected to highlight the effect of AS events on PTC characterization and also provide new insights into refining precise subclassification and improving medical therapy for PTC patients.

Deep learning-based multifeature integration robustly predicts central lymph node metastasis in papillary thyroid cancer

BackgroundFew highly accurate tests can diagnose central lymph node metastasis (CLNM) of papillary thyroid cancer (PTC). Genetic sequencing of tumor tissue has allowed the targeting of certain genetic variants for personalized cancer therapy development.MethodsThis study included 488 patients diagnosed with PTC by ultrasound-guided fine-needle aspiration biopsy, collected clinicopathological data, analyzed the correlation between CLNM and clinicopathological features using univariate analysis and binary logistic regression, and constructed prediction models.ResultsBinary logistic regression analysis showed that age, maximum diameter of thyroid nodules, capsular invasion, and BRAF V600E gene mutation were independent risk factors for CLNM, and statistically significant indicators were included to construct a nomogram prediction model, which had an area under the curve (AUC) of 0.778. A convolutional neural network (CNN) prediction model built with an artificial intelligence (AI) deep learning algorithm achieved AUCs of 0.89 in the training set and 0.78 in the test set, which indicated a high prediction efficacy for CLNM. In addition, the prediction models were validated in the subclinical metastasis and clinical metastasis groups with high sensitivity and specificity, suggesting the broad applicability of the models. Furthermore, CNN prediction models were constructed for patients with nodule diameters less than 1 cm. The AUCs in the training set and test set were 0.87 and 0.76, respectively, indicating high prediction efficacy.ConclusionsThe deep learning-based multifeature integration prediction model provides a reference for the clinical diagnosis and treatment of PTC.

Papillary Carcinoma in a Patient with a Thyroid Nodule: Role of Ultrasonography and its Diagnostic Accuracy

Introduction: While it can be difficult to categorize thyroid lesions, employing ultrasound may enable correct diagnosis, classification, and therapy of thyroid nodules, particularly papillary carcinoma of the thyroid, and assist save unneeded biopsy. Objective: Taking histopathology as the gold standard, assessing the diagnostic precision of ultrasound in the identification of papillary cancer in thyroid nodule patients. Study design: Cross sectional study Study Settings: Department of ENT & Surgery, Jinnah Teaching Hospital, Peshawar Study Duration: This study was conducted from 1st August 2021 till 30th June 2022. Materials and Methods: Patients of both gender who sought assessment for a thyroid nodule were included. On ultrasonography, papillary carcinoma was detected. The gold standard for diagnosing cancers, histology, was used to confirm papillary carcinoma. Using a 2×2 table, diagnostic accuracy was assessed in terms of sensitivity, specificity, PPV, and NPV. Results: Overall 241 participants recruited. The patients were between the ages of 18 and 75. The patients' mean age was 57.80 + 9.245 years. The ratio of men to women was 1.2:1. The ultrasound's sensitivity, specificity, PPV, NPV, and diagnostic accuracy for the diagnosis of papillary thyroid cancer were, respectively, 85.1%, 97.5%, 88.8%, 96.5%, and 95.1%. Conclusion: With clinically significant diagnostic accuracy for the early diagnosis of thyroid papillary carcinoma, ultrasound is a cost-effective, non-invasive diagnostic method that may lessen the need for invasive diagnostic methods like thyroid biopsy. Keywords: Papillary Carcinoma of Thyroid, Ultrasound, Diagnostic Accuracy

Expression Levels of MicroRNA-300/BCL2L11 in Papillary Thyroid Cancer and Their Clinical Diagnostic Values

Introduction: This research aims to explore the expression levels of microRNA (miRNA)-300/BCL-2-like protein 11 (BCL2L11) and their values in the clinical diagnosis of papillary thyroid cancer (PTC). Methods: Pathological tissues that were surgically removed for thyroid disease were selected. miR-300 and BCL2L11 expression levels in the samples were measured. Receiver operating characteristic (ROC) curves were plotted to analyze miR-300 and BCL2L11 predictive values for PTC. Upon silencing miR-300 and silencing BCL2L11 in PTC cells, the corresponding miR-300 and BCL2L11 expression levels were tested, followed by examining PTC cell activities. The targeting relationship of miR-300 and BCL2L11 was detected by the bioinformatics website and luciferase activity assay. Results: miR-300 expression levels were elevated and BCL2L11 expression levels were reduced in PTC tissues. miR-300 and BCL2L11 expression levels in PTC tissues had a correlation with TNM stage and lymph node metastasis. The results of ROC curve revealed that both miR-300 and BCL2L11 had clinical predictive values for PTC. Mechanistically, miR-300 negatively regulated BCL2L11. The functional assays unveiled that silencing miR-300 impeded PTC cell activities, and silencing BCL2L11 induced PTC cell activities. In the rescue experiment, silencing BCL2L11 reversed the impacts of silencing miR-300 on PTC cell development. Conclusion: This study underlines that miR-300 expression is increased and BCL2L11 expression is declined in PTC. miR-300 and BCL2L11 both have clinical predictive values for diagnosing PTC.

A UPLC Q-Exactive Orbitrap Mass Spectrometry-Based Metabolomic Study of Serum and Tumor Tissue in Patients with Papillary Thyroid Cancer

To find the metabolomic characteristics of tumor or para-tumor tissues, and the differences in serums from papillary thyroid cancer (PTC) patients with or without lymph node metastasis. We collected serums of PTC patients with/without lymph node metastasis (SN1/SN0), tumor and adjacent tumor tissues of PTC patients with lymph node metastasis (TN1 and PN1), and without lymph node metastasis (TN0 and PN0). Metabolite detection was performed by ultra-high performance liquid chromatography combined with Q-Exactive orbitrap mass spectrometry (UPLC Q-Exactive). There were 31, 15, differential metabolites in the comparisons of TN1 and PN1, TN0 and PN0, respectively. Seven uniquely increased metabolites and fourteen uniquely decreased metabolites appeared in the lymph node metastasis (TN1 and PN1) group. Meanwhile, the results indicated that four pathways were co-owned pathways in two comparisons (TN1 and PN1, TN0 and PN0), and four unique pathways presented in the lymph node metastasis (TN1 and PN1) group. Common or differential metabolites and metabolic pathways were detected in the lymph node metastasis and non-metastatic group, which might provide novel ways for the diagnosis and treatment of PTC.

MODERN ULTRASOUND IMAGING TECHNOLOGIES IN THE DIAGNOSIS OF PAPILLARY THYROID CANCER

The aim of the study was to determine the opportunities of multiparametric ultrasound in the early detection of papillary thyroid cancer. Examination results of 258 patients with papillary thyroid cancer at the stage of preoperative preparation were analyzed. All patients underwent multiparametric ultrasound examination in grey-scale mode, in color Doppler mapping mode, in compression elastography mode and shear wave elastography, ultrasound with contrast enhancement. In papillary thyroid cancer, "cold" tones prevailed. the velocity of the shear wave was 4.61±1.33 m/s (95% CI), Young's modulus was 63.3±14.7 kPa (95% CI), the elasticity index (strain ratio) was 4.89±1.65 (95% CI) c.u. When assessing the qualitative parameters of ultrasound with contrast enhancement, it was noted that in papillary thyroid cancer, heterogeneous accumulation of ultrasound contrast agent prevailed (54.5%), there was a more pronounced intensive accumulation of ultrasound contrast agent (63.6%). when measuring TPI, the EC indicator was 20.64±4.37 s, PI – 31.08±1.65 dB, PI (DT/2) – 64.00±10.27 s. Thus, the study showed that the complex use of multiparametric ultrasound examination techniques (B-mode, color Doppler mapping, compression elastography, shear wave elastography, ultrasound with contrast enhancement) is highly informative and should be used in the differential diagnosis of papillary thyroid cancer in the preoperative assessment.