Papillary Thyroid Cancer Group Research Articles

Analysis of the Value of Ultrasound Imaging Combined with Serum Indicators in Evaluating the Invasiveness of Papillary Thyroid Carcinoma

Objective: To analyze the value of ultrasound imaging combined with serum indicators in evaluating the invasiveness of papillary thyroid cancer (PTC). Methods: One hundred and fifty patients with papillary thyroid cancer admitted to our hospital from September 2019 to December 2022 were selected. Pathological tissue testing was performed on all patients. According to the size, shape, boundary, internal echo, and characteristics such as microcalcification, the patients were divided into the PTC metastasis group (n = 55) and the PTC group (n = 95). The detection rate of ultrasound imaging combined with serum indicators and the invasiveness of PTC were observed and analyzed. Results: The detection rate of ultrasound imaging combined with serum indicators in both groups was significantly better than that of ultrasound imaging and serum indicators (P < 0.05). The detection rate of ultrasound imaging combined with serum indicators was compared between the groups. The removal rate of the PTC metastasis group was significantly better than that of the PTC group (P < 0.05). The levels of thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroglobulin antibodies (TgAb), and thyroid autoantibodies (TPOAb) in the PTC group were lower than those of the PTC metastasis group (P < 0.05). Conclusion: Ultrasound imaging combined with serum indicators like TSH, Tg, TgAb, and TPOAb has important clinical significance in evaluating the invasiveness of PTC.

Expression and prognosis analysis of integrin subunit α3 (ITGA3) in papillary thyroid cancer

Integrin subunit α3 (ITGA3) is a member of the integrin family and interacts with extracellular matrix proteins. However, there have been few reports regarding the role of ITGA3 in papillary thyroid cancer. The expression levels of ITGA3 were firstly analyzed by bioinformatics tools and in vitro experiments, followed by evaluating its prognostic significance in papillary thyroid cancer patients using Kaplan-Meier, receiver operating characteristic, and Cox regression analyses. Then, cBioportal and GSCA databases were applied to evaluate genetic alterations of ITGA3. Functional enrichment analysis was conducted and the upstream miRNAs of ITGA3 were determined. The results showed that the ITGA3 mRNA and protein levels were higher in the papillary thyroid cancer group than those in the normal group (all P < 0.05). Moreover, ITGA3 performed well in distinguishing the recurrence-free survival (RFS) status and served as an independent prognostic factor of papillary thyroid cancer patients (P < 0.01). Besides, significant relations between ITGA3 and genetic alterations were observed (FDR <0.01). Functional enrichment analysis indicated ECM-receptor interaction and cell adhesion molecules were the shared regulatory pathways. Moreover, ITGA3 might be the target gene of hsa-miR-3129, hsa-miR-181d, hsa-miR-181b, hsa-miR-199a, and hsa-miR-199b. Of note, the ITGA3 mRNA level was reduced after has-miR-199b-3p/5p was overexpressed. In conclusion, ITGA3 could be a reliable biomarker and have potential value in predicting the RFS status of papillary thyroid cancer patients.

TTK is a potential regulator of tumor progression correlated with dedifferentiation and immune cell infiltration in papillary thyroid cancer.

To investigate the role and clinical significance of threonine tyrosine kinase (TTK) in papillary thyroid cancer (PTC). TTK expression in PTC and normal groups were compared using TCGA data and in vitro experiments. The prognostic value of TTK and its possible role in PTC dedifferentiation was evaluated. Next, TTK involvement in PTC occurrence and progression was analyzed via in vitro experiments. Subsequently, analyses of enrichment and immune cell infiltration were conducted to reveal the possible mechanism. Finally, we predicted the target miRNAs followed by performing a luciferase reporter experiment. TTK upregulation was observed in PTC, and its elevated level was significantly related to an unfavorable prognosis (P < 0.05). Interestingly, TTK negatively correlated with thyroid differentiation score (TDS), and patients with higher TDS showed longer survival (all P < 0.05). PTC cell growth, migration, and invasion were inhibited upon TTK knockdown. Besides, TTK was involved in metabolic processes and regulated cell adhesion molecules pathway. Its overexpression was positively associated with immune cell infiltrates (P < 0.05). Moreover, miR-582-5p was an upstream target of TTK. TTK serves as a potential biomarker for tumorigenesis and prognosis in PTC, especially for those that may differentiate into more aggressive thyroid cancers.

THU587 High Prevalence Of Primary Aldosteronism Diagnosis In Patients With Papillary Thyroid Cancer And Hypertension: A Cross-sectional Case-control Study

Abstract Disclosure: A.W. Maciel: None. T. Freitas: None. D.L. Danilovic: None. G.F. Fagundes: None. F. Freitas-Castro: None. L. Santana: None. A. Guimaraes: None. A. Pio-Abreu: None. J. V. Silveira: None. F. Consolim-Colombo: None. L. Bortolotto: None. M.C. Fragoso: None. A. Latronico: None. L. Drager: None. B.B. Mendonca: None. A.O. Hoff: None. M.Q. Almeida: None. Introduction: Aldosterone excess can cause oxidative stress leading to DNA damage in vitro and in vivo. Single case reports demonstrated a coincidence of primary aldosteronism (PA) with different malignancies. A higher prevalence of thyroid nodules and non-toxic multinodular goiter was described in patients with PA compared to those with essential hypertension (HT). A single study showed an association between PA and papillary thyroid cancer (PTC), but without a paired control group. Objective: To assess PA prevalence in a transversal cohort of patients with PTC and HT compared to a paired control group with HT. Methods: In this cross-sectional case-control study, PA was investigated in all patients with PTC and HT (n= 114), regardless of HT severity, under active surveillance at a cancer institute from 2019 to 2022. The control group included 228 (2:1) age-, sex- and body mass index (BMI)-matched individuals from a retrospective cohort of HT previously investigated for PA from 2011 to 2022. Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone ≥10 ng/dL and aldosterone to renin ratio ≥2 ng/dL/μUI/mL. Results: Age, sex and BMI were not statistically different between PTC and control groups, respectively (age 59.8 ± 12 vs. 58.9 ± 12.3 yrs, p= 0.67; 79% vs. 81% women, p= 0.67; BMI 30.7 ± 5.8 vs. 30.8 ± 6.5 Kg/m2, p= 0.98). PA was diagnosed in 35 out of 114 PTC patients with HT. The prevalence of PA in the PTC group (30.5%, confidence interval (IC) 22.6%-40.1%) was significantly higher when compared to the paired control group with HT (11.84%, CI 8.08%-16.93%; p&amp;lt; 0.0001). Although PA prevalence was higher in the PTC group, only 20.2% had stage 3/resistant HT (vs. 38% in the control group, p= 0.003). The number of anti-hypertensive medications was lower in the PTC group compared to controls (2 drugs, 1 to 3 vs. 4 drugs, 3 to 5, respectively; p&amp;lt; 0.001). When analyzing only PA patients in both groups, frequency of stage 3/resistant HT and number of medications were lower in the PTC group (p&amp;lt; 0.001 and p&amp;lt; 0.001, respectively). Although HT was more severe in PA patients without PTC, aldosterone and renin levels were not different in PA patients from PTC and control groups, respectively (p= 0.15 and p= 0.34). Conclusion: PA prevalence was strikingly high among patients with PTC and HT, supporting the recommendation of PA screening in this patient group, regardless of HT severity. Presentation: Thursday, June 15, 2023

Association of serum miR-375, miR-155 and miR-146b levels with distinguish of papillary thyroid cancer from benign thyroid masses among Iranian patients

Background and aimCertain serum levels of microRNAs (miRNAs) throughout the body can be helpful for cancer diagnosis and prognosis. The miRNAs can be secreted from the papillary thyroid cancer (PTC) into the circulatory system. Accordingly, this study aimed to measure the serum levels of miR-146b, miR-155 and miR-375 to evaluate their diagnostic potentials in distinguish of benign from malignant lesions.Materials and methodsThe serum levels of miRNAs were measured by real-time quantitative RT-PCR among100 patients with benign thyroid nodules and 30 patients with PTC.ResultsThe mean miR-375 and miR-155 expression levels in the PTC group were greater when compared with the benign group. The area under the ROC curve (AUC) was estimated at 0.81 for the miR-375 with 0.76% sensitivity and 0.80% specificity to distinguish between benign and PTC lesions. The AUC was calculated to be 0.75 for the miR-155 with 0.69% sensitivity and 0.90% specificity.ConclusionAccording to the results of this study, the serum levels of miR-155 and miR-375 were increased in the patients with PTC, which may be useful as alternative seromarkers for the PTC.

Clinical Implication of Bilateral and Unilateral Multifocality in Papillary Thyroid Carcinoma: A Propensity Score-Matched Study.

Papillary thyroid cancer (PTC) is commonly characterized by multifocality, which is associated with aggressive features and a less favorable prognosis. The current study aimed to compare the clinicopathologic characteristics and long-term oncological outcomes of bilateral and unilateral multifocal PTC. The medical records of 1745 patients with multifocal PTC who underwent thyroid surgery at Seoul St. Mary's Hospital were retrospectively reviewed. The clinicopathological characteristics and recurrence rates were compared based on cancer laterality. Further, 357 patients who underwent total thyroidectomy were matched to investigate the recurrence risk and disease-free survival (DFS). Before propensity score matching (PSM), there was no significant difference in the recurrence rate between the bilateral and unilateral multifocal PTC groups. Cancer laterality was not a predictor of DFS based on the Cox regression analyses. However, after PSM, unilateral multifocality was associated with a significantly high risk of recurrence. Similarly, unilateral multifocality was associated with a significantly poor DFS based on the Kaplan-Meier analysis. Compared with bilateral PTC, unilateral multifocal PTC was associated with a poor DFS. A comprehensive preoperative examination should be performed to detect multifocality before the initial surgical intervention for optimal treatment. Postoperative short-term follow-up is recommended for unilateral multifocal PTC for recurrence surveillance.

Outcomes of Patients with an Intermediate-Risk Group According to the Japanese Risk Classification of Papillary Thyroid Carcinoma

BackgroundThe management of intermediate-risk group of papillary thyroid cancer (PTC) is still vague, particularly regarding whether or not total thyroidectomy, postoperative radioactive iodine ablation (RAI-a), and postoperative TSH suppression are mandatory.MethodsThis retrospective study evaluated 680 PTC patients from 2010 to 2017, who were classified into the three risk groups as low, intermediate, and high-risk groups according to the criteria of the Japanese Association of Endocrine Surgeons (JAES) 2010 and underwent surgery according to the JAES guidelines. We retrospectively collected patient data for analyses of disease-free survivals in the intermediate-risk group patients.ResultsWe performed surgery on 680 PTC patients from 2010 to 2017. Of them, 297 were classified as the intermediate-risk group. DFS was not statistically significantly different in patients with/without total thyroidectomy and postoperative TSH suppression therapy. For RAI-a, DFS (95% confidence interval) at 3, 5, and 8 years were 93.2% (84.6 ~ 97.2), 81.6% (68,3 ~ 90.2), and 70.7% (51.4 ~ 84.6) in patients with postoperative RAI-a and 100%, 100%, and 100% in patients without postoperative RAI-a after total thyroidectomy, respectively. DFS of patients without RAI-a was superior to those with RAI-a (P < 0.0004). Multivariable analysis by stepwise selection method revealed that postoperative RAI-a was a risk factor with a hazard ratio of 5.69. (95% CI 1.998–16.21) (P = 0.001131).ConclusionsOur study did not show the efficacy of RAI-a in patients with intermediate-risk PTC. This study implies that judging the efficacy of adjuvant therapy such as RAI or TSh suppression in intermediate-risk patients is difficult.

Neutrophil-to-Lymphocyte Ratio Is Associated With the Proportion of Poorly Differentiated Components in Papillary Thyroid Carcinoma

IntroductionDiagnosis of poorly differentiated thyroid cancer (PDTC) requires ≥ 50% of poorly differentiated components (PDC) in Japan. However, the optimal cutoff percentage of PDC for PDTC diagnosis remains controversial. Although high neutrophil-to-lymphocyte ratio (NLR) correlates with the aggressiveness of papillary thyroid cancer (PTC), whether NLR is associated with the proportion of PDC in PTC remains unstudied. Materials and methodsPatients with the pure PTC (n = 664), PTC with < 50% PDC (n = 19), or PTC with ≥ 50% PDC (n = 26) who underwent surgery were retrospectively analyzed. Twelve-year disease-specific survival and preoperative NLR were compared among these groups. ResultsTwenty seven patients died from thyroid cancer. The PTC with ≥ 50% PDC group (80.7%) showed significantly worse 12-year disease-specific survival than the pure PTC group (97.2%) (P < 0.001); however, the < 50% PDC group (94.7%) did not (P = 0.91). The PTC with ≥ 50% PDC group had a significantly higher NLR than the pure PTC (P < 0.001) and the PTC with < 50% PDC groups (P < 0.001), whereas there was no significant difference in the NLR between the pure PTC and the PTC with < 50% PDC groups (P = 0.48). ConclusionsPTC with ≥ 50% PDC is more aggressive than either pure PTC or PTC with < 50% PDC, and NLR potentially reflects the PDC proportion. These results support the validity of 50% PDC as a cut-off for PDTC diagnosis and indicate the utility of NLR as a biomarker for PDC proportion.

Association of AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms with papillary thyroid carcinoma: A case-control study.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer which its precise etiology remains unknown. However, environmental and genetic factors contribute to the etiology of PTC. Axis inhibition protein 1 (Axin1) is a scaffold protein that exerts its role as a tumor suppressor. In addition, Cathepsin B (Ctsb) is a cysteine protease with higher expression in several types of tumors. Therefore, the aim of this study was to investigate the possible association of AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms with PTC susceptibility. In total, 156 PTC patients and 158 sex-, age-, and BMI-matched control subjects were enrolled in the study. AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms were genotyped using the PCR-RFLP method. There was a relationship between AXIN1 rs12921862 C/A polymorphism and an increased risk of PTC in all genetic models except the overdominant model. The AXIN1 rs1805105 G/A polymorphism was associated with an increased PTC risk only in codominant and overdominant models. The frequency of AXIN1 Ars12921862 Ars1805105 haplotype was higher in the PTC group and also this haplotype was associated with an increased risk of PTC. Moreover, the AXIN1 rs12921862 C/A polymorphism was not associated with PTC clinical and pathological findings, but AXIN1 rs1805105 G/A polymorphism was associated with almost three folds of larger tumor size (≥1cm). There was no association between CTSB rs12898 G/A polymorphism and PTC and its findings. The AXIN1 rs12921862 C/A and rs1805105 G/A polymorphisms were associated with PTC. AXIN1 rs1805105 G/A polymorphism was associated with higher tumor size.

Preconditioning of the immune system modulates the response of papillary thyroid cancer to immune checkpoint inhibitors

BackgroundThe response of solid tumors such as papillary thyroid cancer (PTC) to immune checkpoint inhibitors (ICIs) is highly variable. The biological basis of this variability remains unknown.MethodsTo test the hypothesis...

Association Between Vaspin Gene Polymorphism and Serum Vaspin Level in Women With Papillary Thyroid Cancer and Multinodular Goiter

Background and Objectives: Vaspin is a novel adipocytokine. Various studies have shown that vaspin is associated with many types of cancer. This study aims to determine the association of vaspin rs2236242 gene polymorphism with vaspin level in women with papillary thyroid cancer (PTC) and Multinodular goiter (MNG). Methods: In this case-control study participants were 134 women. They were divided into three groups; PTC (n=49), MNG (n=30) and control (n=55). Ten milliliter peripheral blood samples were taken from participants, 5 ml was used for DNA extraction and 5 ml for preparation of serum. The vaspin level was measured by Sandwich ELISA kit. The genotype determination of vaspin rs2236242 polymorphism was done using the tetra primer-amplification refractory mutation system/polymerase chain reaction method. Results: There were no significant difference in serum vaspin level among the three groups. There was no significant association between genotypes of vaspin rs2236242 polymorphism and serum vaspin level in any groups. Logistic regression analysis showed that the difference in the frequency of the genotypes of rs2236242 polymorphism in the MNG group was significant compared to the control group. The TA genotype showed a protective effect against PTC and MNG (P&lt;0.05). Conclusion: There is no significant difference in vaspin level between PTC, MNG and control groups. There is no association between rs2236242 gene polymorphism and serum vaspin level. The TA genotype of rs2236242 has a protective effect against MNG.

The Role of TSHR, PTEN and RASSF1A Promoters' Methylation Status for Non-Invasive Detection of Papillary Thyroid Carcinoma.

Aim: We investigated whether a difference exists between TSHR, PTEN and RASSF1A methylation status in plasma of subjects with papillary thyroid cancer (PTC). Methods: Peripheral blood samples were collected from 68 patients with PTC and 86 healthy controls (HC). Thyroid cancer tissue and corresponding adjacent normal tissue methylation levels were analyzed. DNA methylation level changes in TSHR, PTEN and RASSF1A genes were analyzed by quantitative methylation-sensitive polymerase chain reaction. Results: We observed that the methylation level of TSHR was significantly higher in the thyroid cancer tissue compared to adjacent normal tissue (p = 0.040). TSHR methylation levels in the PTC group plasma samples were significantly higher compared to HC (p = 0.022). After surgery, PTC plasma samples showed lower TSHR and PTEN methylation levels compared to the levels before surgery (p = 0.003, p = 0.031, respectively). The TSHR methylation level was significantly higher in PTC with larger tumor size (>2 cm) (p < 0.001), and lymph node metastases (p = 0.01), lymphovascular invasion (p = 0.02) and multifocality (p = 0.013) 0ROC analysis revealed that the TSHR methylation level provides high accuracy in distinguishing PTC from HC (p = 0.022, AUC of 0.616). Conclusion: TSHR methylation in peripheral blood samples is expected to be a sensitive and specific minimally invasive tool for the diagnosis of PTC, especially in combination with other diagnostic means.

Diagnostic Value of Circulating Cell-free DNA in Patients With Papillary Thyroid Cancer.

We investigated whether the occurrence and development of papillary thyroid cancer (PTC) might be predicted using levels of circulating cell-free DNA (cfDNA). The peripheral blood samples were collected from 68 patients with PTC, 31 patients with nodular goiter (NG), and 86 healthy controls (HC). The concentration of cfDNA was measured by qPCR using three primer sets: β-actin99, β-actin394 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in plasma samples. It was demonstrated that plasma β-actin99 and β-actin394 in the PTC group were significantly higher compared to HC (p<0.05 and p<0.001, respectively). The cfDNA integrity index was significantly higher in the PTC patients compared to HC and NG (p<0.001, p<0.05, respectively). The cfDNA concentration in the NG group was significantly higher than in the PTC (p<0.05 and p<0.001, respectively). Moreover, in most PTC patients with suppressed thyroglobulin, the β-actin394 and cfDNA integrity index was significantly decreased after surgery (p<0.05 and p<0.001, respectively). ROC analysis revealed that cfDNA integrity index can be used as a potential marker in distinguishing PTC from HC (AUC 0.901, p<0.001) and NG (AUC 0.629, p<0.05). Increased concentration of cfDNA β-actin99 and β-actin394 may be a valuable biomarker that differentiates PTC patients from HC. Also, an increased cfDNA integrity index may be a suitable parameter which differentiates PTC patients from NG and HC.

Recurrent Laryngeal Nerve Injury in Thermal Ablation of Thyroid Nodules-Risk Factors and Cause Analysis.

Recurrent laryngeal nerve (RLN) injury is a complication of thermal thyroid nodule treatment. We investigated the influencing factors of RLN injury in patients who underwent thermal ablation of thyroid nodules. The data of 1004 patients (252 male, 752 female; median age 44 years) who underwent thermal thyroid nodule ablation were retrospectively reviewed. Patients were divided into benign cystic, benign solid, and papillary thyroid cancer (PTC) groups. The parameters related to RLN injury were analyzed, including the largest diameter, location of the nodules, and shortest distance of the nodule to thyroid capsule and tracheoesophageal groove (TEG). Univariate and multivariate analyses were performed to select risk factors for RLN injury. The RLN injury rate was higher in PTC (6.3%) than in benign cystic (1.2%, P = 0.019) and solid nodules (2.9%, P = 0.018). PTC subgroup analysis showed that the RLN injury rate was higher in T1b (10.7%) and T2 (28.6%) PTC than in T1a PTC (5.0%, P < 0.05). In the PTC group, TEG distance, anterior capsule distance, median capsule distance, posterior capsule distance, and maximum nodule diameter were risk factors for RLN injury. The logistic regression fitting of the nomogram showed high prediction efficiency (C-Index 0.876). The main cause of RLN injury was insufficient medial isolating fluid (MIF). The safety thicknesses of MIF for benign cystic, benign solid, and PTC nodules were 3.1 mm, 3.7 mm, and 3.9 mm, respectively. Several risk factors for RLN injury should be considered before thermal ablation of thyroid nodules. The RLN injury rate could be predicted with the nomogram.

Frequency of hashimoto thyroiditis in papillary thyroid cancer patients and its impact on their Outcome.

Hashimoto thyroiditis (HT) is an autoimmune disorder of thyroid gland and is the most common cause of hypothyroidism. Its association with thyroid lymphoma is well established but with papillary thyroid cancer (PTC), the studies have shown inconsistent results. It is a retrospective review of papillary thyroid cancer patients and 213 participants were included for final analysis. They were divided in two groups, based on presence or absence of Hashimoto thyroiditis. We noted their demographic details, histopathological diagnosis, presence of thyroid autoantibodies, TNM staging, outcome and duration of follow up. The frequency of Hashimoto thyroiditis in papillary thyroid cancer patients was found to be 34.27% (73). In Hashimoto thyroiditis and PTC patients, more patients were in T1 and T2 stage, i.e., 27.4% and 38.4% as compared to PTC alone group, who had more patients with T3 and T4 disease 44.3% and 5% respectively. Although lymph node metastasis was more common in PTC with Hashimoto thyroiditis 56.2%, but distant metastasis was observed more in isolated PTC group 14.3%. Cure was observed in 75.3% and 47.1% in PTC patients with and without Hashimoto thyroiditis respectively. While 22.9% patients having isolated PTC had persistent disease as compared to 6.8% when PTC was accompanied with Hashimoto thyroiditis. The papillary thyroid cancer patient who had concomitant Hashimoto thyroiditis, had a less aggressive disease in terms of T stage and distant metastasis and they had a better outcome in terms of higher cure rate and less persistent disease as compared to the papillary thyroid cancer without Hashimoto thyroiditis.

Diversity of complement activation in different thyroid diseases

ObjectiveTo investigate complement components expression in both thyroid tissues and serum from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), and papillary thyroid cancer (PTC). MethodsC1q, mannose binding lectin (MBL), Bb, C4d, C3d and membrane attack complex (MAC) (C5b-9) deposition and complement regulate proteins (CD46, CD55 and CD59) expression in thyroid tissues from HT, GD, PTC, and control groups were examined by IHC. C1q, MBL, Bb, C4d, C3a, and soluble C5b-9 (sC5b-9) serum levels in the HT, GD, PTC, and healthy donor (HD) groups were measured by ELISAs. ResultsMAC deposition was detected in thyroid tissues in the HT, GD and PTC groups, but not the control group. MBL, Bb, C4d, C3d and MAC staining intensities in thyroid tissues were significantly higher in the HT and PTC groups than in the control group (all P < 0.05). The C1q level was higher in HT tissues than in control tissues (both P < 0.05). No complement component had a significant difference in staining intensities between the GD and control groups. CD55 and CD59 expression levels in thyroid tissues were higher in the PTC group than in the HT, GD and control groups (all P < 0.05). Similarly, CD46 levels were higher in HT tissues than in control tissues. Bb, C4d, C3a and sC5b-9 serum levels were significantly increased in HT, GD and PTC patients compared with HDs (all P < 0.05). ConclusionComplement is overactivated in HT and PTC, but not in GD. All the three pathways are activated in HT, and the MBL and alternative complement pathways are activated in PTC. These distinct complement activation profiles may participate in HT, GD and PTC pathogenesis.

Identification of Transcriptional Pattern Related to Immune Cell Infiltration With Gene Co-Expression Network in Papillary Thyroid Cancer.

BackgroundA growing body of evidence suggests that immune cell infiltration in cancer is closely related to clinical outcomes. However, there is still a lack of research on papillary thyroid cancer (PTC).MethodsBased on single-sample gene set enrichment analysis (SSGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) tool, the infiltration level of immune cell and key modules and genes associated with the level of immune cell infiltration were identified using PTC gene expression data from The Cancer Genome Atlas (TCGA) database. In addition, the co-expression network and protein-protein interactions network analysis were used to identify the hub genes. Moreover, the immunological and clinical characteristics of these hub genes were verified in TCGA and GSE35570 datasets and quantitative real-time polymerase chain reaction (PCR). Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of hub genes.ResultsActivated B cell, activated dendritic cell, CD56bright natural killer cell, CD56dim natural killer cell, Eosinophil, Gamma delta T cell, Immature dendritic cell, Macrophage, Mast cell, Monocyte, Natural killer cell, Neutrophil and Type 17 T helper cell were significantly changed between PTC and adjacent normal groups. WGCNA results showed that the black model had the highest correlation with the infiltration level of activated dendritic cells. We found 14 hub genes whose expression correlated to the infiltration level of activated dendritic cells in both TCGA and GSE35570 datasets. After validation in the TCGA dataset, the expression level of only 5 genes (C1QA, HCK, HLA-DRA, ITGB2 and TYROBP) in 14 hub genes were differentially expressed between PTC and adjacent normal groups. Meanwhile, the expression levels of these 5 hub genes were successfully validated in GSE35570 dataset. Quantitative real-time PCR results showed the expression of these 4 hub genes (except C1QA) was consistent with the results in TCGA and GSE35570 dataset. Finally, these 4 hub genes had diagnostic value to distinguish PTC and adjacent normal controls.ConclusionsHCK, HLA-DRA, ITGB2 and TYROBP may be key diagnostic biomarkers and immunotherapy targets in PTC.

Importance and Risk Prediction of ABO Blood Group and Rh Factor in Papillary Thyroid Cancer

Objective: There are limited data in the literature regarding the potentialrelationship between thyroid cancer and ABO blood types and Rh factor.The aim of our study was to investigate whether papillary thyroid cancer(PTC) is associated with blood type.Materials and Methods: The present study included patients who presented to Dicle University Faculty of Medicine between June 2009 andDecember 2020 and were diagnosed with PTC as a result of postoperative(thyroidectomy) histopathological analysis. The control group consisted ofindividuals whose blood type was analyzed at a random blood center.Results: Of the 223 patients diagnosed with PTC, 163 (73.1%) were females and 60 (26.9%) were males. In the comparison of patients based onABO blood types and Rh factor, A Rh positive blood type was found 31%less frequently in the PTC group compared with the control group, and thusit was associated with a lower risk of PTC (OR:0.69; 95% Confidence Interval: 0.50–0.96, p=0.029).Conclusions: In our study, we found A Rh positive blood type to be significantly less frequent among patients with PTC. A Rh positive blood type canbe considered as a protective factor indicating a reduced risk of PTC.

The Role of Preoperative Complete Blood Count Indices in the Distinction of Papillary Thyroid Cancer from Nodular Goiter

Aim: Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (respectively, NLR and PLR) have been associated with poor prognosis in various cancers. This study was conducted to investigate PLR and NLR in patients with papillary thyroid cancer (PTC) and nodular goiter (NG). Materials and Methods: Patients who had undergone thyroidectomy at our center were reviewed and the demographic, clinical and histopathological characteristics of patients with PTC or NG were recorded. Hemogram (complete blood count) results were used to calculate NLR and PLR. Results: The groups were similar with respect to age, gender and thyroiditis characteristics. The NG group was found to have significantly larger gland size compared to the PTC group. NLR and PLR values were similar in the two groups (p&gt;0.05 for both). Conclusion: PLR and NLR appear to be exceedingly similar in PTC and NG, and therefore, they cannot be used to distinguish between PTC and NG. However, it may be valuable to conduct future studies that take into account lesion size when comparing these parameters in thyroid nodules.

TNF-α May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis.

Simple SummaryRecent evidence shows that autoimmune thyroiditis (AIT) may impair the uptake of radioiodine (131I), altering the success of attempted remnant ablation in papillary thyroid cancer (PTC), but the cause is not clear. Finding the mechanisms that govern immune cells during the 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale for these reports. Our study was conducted on female patients admitted for 131I therapy. In the PTC group, 131I therapy modulates the production of cytokines in situ, increasing the antitumor immune response accordingly. On the contrary, in the presence of chronic inflammation due to AIT, 131I therapy amplifies innate immunity, leading to a weaker development of adaptive, specific immunity.Autoimmune thyroiditis (AIT) may impair radioiodine (131I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of 131I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after 131I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after 131I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after 131I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = −0.62, p < 0.001 and r = −0.58, p < 0.001). Our results demonstrate that TNF-α may exert different antitumor effects in response to 131I therapy depending on the patient’s immune profile.