Features Of Papillary Thyroid Cancer Research Articles

12327 Presenting Features of Papillary Thyroid Cancer with Hobnail Histology and Factors Associated with Advanced Disease at Presentation

Abstract Disclosure: S.K. Majumdar: None. J. Sinard: None. The Hobnail subtype of papillary thyroid cancer (PTC) is reported to be a rare form of PTC that manifests with higher rates of extrathyroidal extension, metastases, disease recurrence, and mortality, when compared to classic PTC. We set out to characterize the clinical manifestations and initial pathologic findings of patients with PTC and hobnail histology at our institution. A retrospective search of pathology records from 1/2014 through 1/2024 was conducted to identify rare thyroid cancer variants including those with hobnail histology. An electronic medical record review was then performed to collect clinical information. The study was approved by our institutional IRB. A total of 15 patients with PTC of the hobnail subtype (≥ 30% features) or with hobnail features (< 30%) were identified: 8 hobnail subtype, 5 having hobnail features, 1 had hobnail and oncocytic features, 1 had hobnail and tall cell features. Sixty percent were female, mean age 50.6 years (SD 16.4), 67% white, 27% Hispanic, 6% black. Mean BMI was 29.4 kg/m^2 (SD 5.4), 33% had a history of prior or current smoking. Cancers were found incidentally in 33% of cases (3 after physical exam noting goiter or nodule), 53% presented with a newly noticed neck lesion, one of these presented with hoarseness and cough from tracheal invasion which was found later at surgery. Mean tumor size 2.65 cm (SD 1.7), 13 patients had 1 or more lymph nodes removed with at least one node being positive in 77% of cases. Rates of lymphatic invasion were 73% (33% extensive), vascular invasion 13%, and 13% had gross extrathyroidal extension. After initial surgery 60% had stage 1 disease, 27% stage 2, and 13% stage 3. One patient was changed to stage 4 upon the later discovery of lung metastases and this patient had 30% tall cell features on pathology. Three patients had T3 or T4 tumors, all of whom were from minority and vulnerable populations (2 non-English speaking Hispanic, 1 Black with mental illness), had significantly higher BMI than others (36.2 ± 4 vs 27.2 ± 4.5, p = 0.01), and tended to be older (67 ± 9.5 vs 46.5 ± 16, p = 0.057 ns). Long term follow up was limited since hobnail histology was only found in reports beginning in 2017 and became more frequent in 2022 and 2023. Although limited by case number, our findings show that patients who presented with the most advanced disease were from vulnerable populations, were older, and had higher BMI’s than those with lower stage disease. Also, coexistence of other variants, like tall cell changes, may impact presentation. Therefore, while PTC with hobnail histology is typically associated with more advanced disease presentations, psychosocial and other factors appeared to explain higher stage disease at presentation in our series. Presentation: 6/3/2024

Association of thyroid autoantibodies with aggressive characteristics of papillary thyroid cancer: a case-control study

PurposeAlthough the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown.Patients and methodsWe conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC.ResultsIn total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes.ConclusionElevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis.

Interplay of metabolic dysfunction-associated fatty liver disease and papillary thyroid carcinoma: insights from a Chinese cohort.

Thyroid cancer is one of a set of extrahepatic cancers that closely linked to metabolic dysfunction-associated fatty liver disease (MAFLD). However, the connection between MAFLD and the characteristics of papillary thyroid cancer (PTC) remains unexplored. Between Jan 2020 and Oct 2022, surgical cases of PTC patients were examined at the first Affiliated Hospital of Wenzhou Medical University. Clinical data extracted from the electronic medical system underwent a rigorous comparison between two groups, classified based on MAFLD criteria, using logistic regression analysis. In this study of 4,410 PTC patients, 18.3% had MAFLD. MAFLD emerged as a distinct risk factor for lymph node metastasis (OR = 1.230, 95% CI 1.018-1.487) in this cohort, especially in females (OR = 1.321, 95% CI 1.026-1.702) and those with BMI ≥ 23kg/m2 (OR = 1.232, 95% CI 1.004-1.511). The presence of MAFLD was found to significantly elevate the risk of BRAF V600E mutation in both subgroups characterized by FIB-4 score ≥ 1.3 (OR = 1.968, 95% CI 1.107-3.496) and BMI < 23kg/m2 (OR = 2.584, 95% CI 1.012-6.601). Moreover, among the subset of individuals without non-alcoholic fatty liver disease (NAFLD), it was noted that MAFLD considerably increased the likelihood of tumor multifocality (OR = 1.697, 95% CI 1.111-2.592). Nevertheless, MAFLD did not exhibit any correlation with increased tumor size, extra-thyroidal extension (ETE), or later TNM stage in PTC. In this cross-sectional study, we discovered a significant association between MAFLD and increased occurrences of lymph node metastasis. Furthermore, MAFLD was linked to a higher chance of BRAF V600E mutation and the presence of multiple tumors in certain subgroups.

Influence of MiR-126-3p and MiR-146a-5p Dysregulation on The Risk and Clinicopathological Features of Papillary Thyroid Cancer in Patients with Thyroid Nodules

Influence of MiR-126-3p and MiR-146a-5p Dysregulation on The Risk and Clinicopathological Features of Papillary Thyroid Cancer in Patients with Thyroid Nodules

Correlation analysis between BRAFV600E mutation and ultrasonic and clinical features of papillary thyroid cancer

PurposeThe study investigates the value of the BRAFV600E mutation in determining the aggressiveness of papillary thyroid cancer (PTC) and its correlation with ultrasound features. MethodsThe study selected 176 patients with BRAFV600E mutation and 80 without the mutation who underwent surgery at Guangxi Medical University Cancer Hospital. Clinical and pathological data were collected, focusing on BRAFV600E mutations and associated ultrasonic features. Correlation analysis, as well as univariate and multivariate logistic regression analysis, were conducted to identify independent risk factors for BRAFV600E mutation. The results were verified using a nomogram model. ResultsThe analysis results indicate that the BRAFV600E mutation correlates with tumor size, nodule size, taller-than-wide shape, margin, and shape of papillary thyroid cancer. The receiver operating characteristic curve was used to analyze the diagnostic effect of these features on BRAFV600E mutation. The results showed that nodule size had the most significant area under the curve (AUC = 0.665). Univariate and multivariate logistic regression analyses revealed that taller-than-wide shape ≥1, ill-defined margin, irregular shape, nodule size (≤1.40 cm), TT4 (>98.67 nmol/L), and FT3 (<4.14 pmol/L) were independent risk factors for BRAFV600E mutation. While considering all these factors in the nomogram, the Concordance index (C-index) remained high at 0.764. This suggests that the model has a good predictive effect. ConclusionUltrasound features including nodule size, taller-than-wide shape ≥1, ill-defined margins, irregular shape, higher TT4 levels, and lower FT3 levels were associated with papillary thyroid cancer aggressiveness and BRAFV600E mutation.

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.

Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids.

Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual responses to therapies. Here, using mESC-derived thyroid organoids, we developed a BrafV637E-inducible model able to recapitulate the features of papillary thyroid cancer in vitro. Overexpression of the murine BrafV637E mutation, equivalent to BrafV600E in humans, rapidly triggers to MAPK activation, cell dedifferentiation, and disruption of follicular organization. BrafV637E-expressing organoids show a transcriptomic signature for p53, focal adhesion, ECM-receptor interactions, EMT, and inflammatory signaling pathways. Finally, PTC-like thyroid organoids were used for drug screening assays. The combination of MAPK and PI3K inhibitors reversed BrafV637E oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro. Our results demonstrate that pluripotent stem cells-derived thyroid cancer organoids can mimic tumor development and features while providing an efficient tool for testing novel targeted therapies.

The association between serum selenium levels and pathological features of papillary thyroid cancer in 284 patients.

The relationship between serum selenium levels and papillary thyroid cancer (PTC), especially the pathological features, still remains controversial. We conducted this study to investigate the relationship between serum selenium levels and PTC in a Chinese population. Cross-sectional data of 284 patients with PTC were collected from the First Affiliated Hospital of Shandong First Medical University. The general clinical characteristics, serum selenium levels, and tumor pathological features were described in PTC. The association between serum selenium levels and pathological features in PTC was analyzed using SPSS 26.0 statistical software. Our results showed that the median serum selenium level was 79.15 μg/L (IQR: 71.00 - 86.98 μg/L) in PTC patients. Serum selenium levels were lower in females than males (p = 0.035). Serum selenium levels were negatively correlated with the number of lymph node metastases (p = 0.048). High serum selenium (OR = 0.397, 95%CI: 0.217 - 0.725) and diastolic blood pressure (OR = 1.028, 95%CI: 1.005 - 1.051) were related factors for the incidence of bilateral tumors. High serum selenium (OR = 0.320, 95%CI: 0.166 - 0.617) and diastolic blood pressure (OR = 1.066, 95%CI: 1.031 - 1.103) were related factors for tumor multifocal incidence. The serum selenium levels of PTC patients in females were lower than males. High serum selenium levels might be a protective factor in PTC patients. Further research is necessary to better understand the influence of selenium on PTC progression.

Serum sex hormones correlate with pathological features of papillary thyroid cancer

PurposeSex hormones are thought to be responsible for the unique gender differences in papillary thyroid cancer(PTC). Most previous studies on these have focused on the expression of estrogen receptors, or have been limited to animal studies. The aim of our study was to explore the relationship between serum sex hormones and the pathological features of PTC in the clinical setting, as further evidence of the role of sex hormones in PTC.MethodsRetrospective data analysis of patients who underwent thyroid surgery at the Department of Thyroid Surgery, Nanjing Drum Tower Hospital from January 2022 to September 2022 Correlation between serum sex hormone and pathological features was analyzed in male patients and in menopausal female patients. Serum sex hormones include luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E2), total testosterone(TT), progesterone(P), and prolactin(PRL). Tumor pathological characteristics include the number and size of tumor, presence of extrathyroidal extension(ETE), presence of lymph node metastasis(LNM).ResultsPreoperative serum E2 in male patients was positively correlated with tumor size in PTC, LH was negatively correlated with LNM, while TT and P were negatively correlated with ETE. Similar findings were not observed in menopausal female patients.ConclusionWe observed that serum sex hormones correlate with the pathological features of PTC in male patients, for the first time in a clinical study. High serum estrogens may be a risk factor for PTC, while androgens are the opposite. This somewhat corroborates previous research and provides new variables for future PTC prediction models.

Three-dimensional ultrasound-based radiomics nomogram for the prediction of extrathyroidal extension features in papillary thyroid cancer.

To develop and validate a three-dimensional ultrasound (3D US) radiomics nomogram for the preoperative prediction of extrathyroidal extension (ETE) in papillary thyroid cancer (PTC). This retrospective study included 168 patients with surgically proven PTC (non-ETE, n = 90; ETE, n = 78) who were divided into training (n = 117) and validation (n = 51) cohorts by a random stratified sampling strategy. The regions of interest (ROIs) were obtained manually from 3D US images. A larger number of radiomic features were automatically extracted. Finally, a nomogram was built, incorporating the radiomics scores and selected clinical predictors. Receiver operating characteristic (ROC) curves were performed to validate the capability of the nomogram on both the training and validation sets. The nomogram models were compared with conventional US models. The DeLong test was adopted to compare different ROC curves. The area under the receiver operating characteristic curve (AUC) of the radiologist was 0.67 [95% confidence interval (CI), 0.580-0.757] in the training cohort and 0.62 (95% CI, 0.467-0.746) in the validation cohort. Sixteen features from 3D US images were used to build the radiomics signature. The radiomics nomogram, which incorporated the radiomics signature, tumor location, and tumor size showed good calibration and discrimination in the training cohort (AUC, 0.810; 95% CI, 0.727-0.876) and the validation cohort (AUC, 0.798; 95% CI, 0.662-0.897). The result suggested that the diagnostic efficiency of the 3D US-based radiomics nomogram was better than that of the radiologist and it had a favorable discriminate performance with a higher AUC (DeLong test: p < 0.05). The 3D US-based radiomics signature nomogram, a noninvasive preoperative prediction method that incorporates tumor location and tumor size, presented more advantages over radiologist-reported ETE statuses for PTC.

Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype.

Genotyping is fundamental in papillary thyroid cancer (PTC) and helps to enhance diagnosis and prognosis and determine appropriate treatments. The phenotype-genotype association in PTC was previously studied, with BRAF V600E characterizing classic PTC and tall-cell PTC and RAS mutations characterizing follicular-variant PTC. In clinic, some non-classical histological subtypes of PTC were also identified, however, their genotype remains unclear. In this study, we collected samples of these non-classical PTC after the exclusion of classic phenotypes and examined their phenotypes, genotype and the relationship between phenotype and genotype. We screened out non-classical PTC by excluding classical PTC from 1,059 different thyroid samples, and a total of 24 cases was obtained and described from the morphological features, which is rare in differentiated PTC. DNA/RNA sequencing was performed using 18 available samples to describe the genetic features. PTC with the non-classical phenotype were characterized cuboidal to low columnar tumor cells with subtle nuclear features of PTC and without discernible nuclear elongation, concurrently with dense microfollicles, delicate papillae or solid nodules with delicate fibrovascular cores. They were associated with lymphatic vessel invasion (P<0.001) but not with a worse prognosis (P=0.791). Gene fusions were identified in 14 of 18 (77.8%) cases, including eight fusions of NTRK and six fusions of RET. The high percentage of fusions in this papillary thyroid cancer subgroup suggested a correlation of gene fusions with the phenotype that does not belong to the BRAF V600E-mutant or RAS-mutant group. Our study retrospectively screened a large cohort of different thyroid tissue samples, and presented the histopathological and genetic features of a non-classical phenotype of PTC from 24 patients. It may contribute to diagnose in PTC, and patients of these non-classical phenotype may benefit from targeted therapy, compared to a natural patient cohort without selection.

The Prognostic Significance of BRAF Gene Analysis in Children and Adolescents with Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis

Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). Mutated BRAF is proposed as a prognostic tool in adult PTC. We conducted a systematic review and meta-analysis evaluating the association of mutated BRAF gene and prognostic clinicopathological characteristics of PTC in children/adolescents. Systematic search for relevant studies included PubMed, MEDLINE, Scopus, clinicaltrials.gov and Cochrane Library. Pooled estimates of odds ratios for categorical data and mean difference for continuous outcomes were calculated using random/fixed-effect meta-analytic models. BRAFV600E mutation presents a pooled pediatric/adolescent prevalence of 33.12%. Distant metastasis is significantly associated with mutated BRAF gene (OR = 0.32, 95% CI = 0.16-0.61, p = 0.001). Tumor size (MD = -0.24, 95% CI = -0.62-0.135, p = 0.21), multifocality (OR = 1.13, 95% CI = 0.65-2.34, p = 0.74), vascular invasion (OR = 1.17, 95% CI = 0.67-2.05, p = 0.57), lymph node metastasis (OR = 0.92, 95% CI = 0.63-1.33, p = 0.66), extra-thyroid extension (OR = 0.78, 95% CI = 0.53-1.13, p = 0.19) and tumor recurrence (OR = 1.66, 95% CI = 0.68-4.21, p = 0.376) presented no association or risk with BRAF mutation among pediatric/adolescent PTC. Mutated BRAF gene in children and adolescents is less common than in adults. Mutation in BRAF relates significantly to distant metastasis among children/adolescents with PTC.

Histological Variants of Papillary Thyroid Cancer in Relation to Clinical and Morphological Parameters and Prognosis

The correlation of histological features of papillary thyroid cancer with clinical and morphological prognostic factors and cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center (25 cases with lethal outcome and 64 follow-up controls). Significant variability was revealed in the histological structure of papillary thyroid cancer with the prevalence of classic (62%) and less frequent follicular (19%), tall cell (8%), and solid (7%) variants. In comparison with the classic variant, the solid variant was more often associated with male sex and large tumor size; follicular and tall cell variant was associated with more frequent metastases to regional lymph nodes; follicular and solid variants were associated with an increased proportion of cases with disease stages III-IV. The main differences reflecting the effect of histological factor on the disease outcome were associated with the solid variant of papillary thyroid cancer that was detected in 21% of lethal cases and only in 2% of control subjects. The detection of this variant can be of importance as an additional prognostic factor of the postoperative survival in papillary thyroid cancer.

Genetic and clinical profiles of 160 papillary thyroid cancers with lateral neck lymph node metastasis.

Lymph node metastasis is widespread in papillary thyroid cancer (PTC). Patients are more vulnerable than those with central lymph node metastasis if they have lateral neck lymph node metastasis (LLNM). There are few researches focus on the correlation between clinical characteristics and genetic profile of PTC with LLNM. In this study, we aimed to analyze the clinical and genetic features of PTC with LLNM. A total of 160 primary tumor samples derived from PTC patients with LLNM were involved. Targeted next-generation sequencing was carried out on all samples with 57 known thyroid-cancer-related genes. The associations between genomic alternations and clinical characteristics of PTC with LLNM were statistically evaluated. The median age of patients was 37 years, ranging from 5 to 77 years and the female/male ratio was 1.86. The most frequently altered genes in our series were BRAF mutation (68%), followed by RET fusion (17%), TERT promoter mutation (5%) and PIK3CA mutation (2%). To be noted, all PTC patients with LLNM of TERT promoter mutations appeared along with BRAF mutations (8/8) and half of them experienced a relapse. Intriguingly, we found more metastatic lymph nodes in patients with RET fusion, but there was no statistically significant difference in metastatic lymph node ratio than those with BRAF mutation or without mutation. A high rate of gene fusion (70%) was found in the pediatric population, with aggressive late-onset disease. PTC patients with LLNM is characterized by a high rate of BRAF mutation. Due to the observed clinicopathological differences in those patients among different alterations, further prospective studies are needed to verify our results and to evaluate the most suitable treatment strategies.

Clinical significance of extrathyroidal extension to major vessels in papillary thyroid carcinoma.

Gross extrathyroidal extension (gETE) into major vessel is considered the most advanced stage of the locally advanced papillary thyroid cancer (PTC). Surgical intervention may not benefit some patients at this disease stage or even result in intraoperative death due to massive hemorrhage; however, it is still considered an effective strategy for most cases. The lack of description for this challenging invasion in PTC warrants detailed characterization of its pattern, risk factors, optimal surgical method, and prognostic value. In total, 3127 patients diagnosed as having PTC were enrolled and categorized into two the following groups, namely the major vessel invasion (MVI) group (n = 30) and the control group (n = 3097). Data regarding clinicopathological and demographic characteristics, vascular invasion sites, postoperative complications, locoregional recurrence, distant metastasis, and surgical strategies were collected. Predictive disease-free survival (DFS) was also compared between the two groups. MVI was independently associated with invasion of the esophageal extension, age < 55years, tumor size > 1cm, lateral lymph node metastasis, and distant metastasis (P = 0.00; P = 0.01; 0.05; P = 0.00; P = 0.00, respectively). The difference in the predictive DFS between the two groups was significant (P = 0.00), and the difference remained significant even in patients with ETE when compared with patients without ETE (P = 0.00). Additionally, predictive DFS did not differ significantly between patients who received vessel repairment and those who received vessel resection (P = 0.28). This study first characterized the gross MVI pattern exhibited by PTC and the risk factors for MVI. Additionally, it demonstrated the DFS of patients with PTC. Extensive gross MVI significantly worsened the biological characteristics of PTC. Regardless of the high risk and difficulty of the operation, patients still benefited from the surgical intervention, and vessel repairment may be the optimal surgical strategy.

Preoperative voice analysis and survival outcomes in papillary thyroid cancer with recurrent laryngeal nerve invasion.

To investigate the clinicopathological characteristics of papillary thyroid cancer (PTC) and identify risk factors for postoperative recurrence of PTC with recurrent laryngeal nerve (RLN) involvement. In total, 171 patients (112 women and 59 men, age: 18-80 years, and 65 patients aged ≥ 55) with T4a PTC with RLN involvement, treated at Beijing Tongren Hospital, Capital Medical University, from January 2006 to December 2020, were retrospectively examined. Clinicopathological characteristics, including voice analysis results, and survival outcomes were assessed. The Mann-Whitney U and Kruskal-Wallis H tests were used to analyze differences in acoustic parameters. The Kaplan-Meier method was used to calculate the overall survival (OS) and recurrence-free (RFS) rates. Univariate and multivariate Cox regression analyses were performed of the clinical data. The postoperative follow-up period ranged from 12 to 196 months (mean: 66.18 months). Of the 171 patients, 16 had recurrence and 8 died of thyroid-related diseases. The 5-year OS rate was 95.22%. The 5-year RFS rate was 89.38%. Jitter and shimmer were higher and maximum phonation time was shorter in patients with preoperative vocal cord paralysis (VCP) than in those without RLN involvement, and in those with RLN involvement but without preoperative VCP. Acoustic parameters were similar in patients with no preoperative VCP and those without RLN involvement. Voice analysis results did not differ between cases with RLN adhesion and RLN invasion. Univariate analysis showed that age at onset ≥ 55 years, preoperative RLN palsy, and esophageal invasion were risk factors for postoperative recurrence of PTC with RLN involvement. Multivariate analysis showed that onset age ≥ 55 years (OR 4.52, 95% confidence interval: 1.44-14.19, P = 0.010) was an independent risk factor for recurrence. PTC patients with RLN invasion can achieve good outcomes. Preoperative voice analysis may offer insights into RLN function. Age of onset ≥ 55 years is an independent risk factor for postoperative recurrence in T4a PTC patients.

Integrated analysis of fibroblasts molecular features in papillary thyroid cancer combining single-cell and bulk RNA sequencing technology.

Papillary thyroid cancer (PTC) is the most common pathological type of thyroid cancer with a high incidence globally. Increasing evidence reported that fibroblasts infiltration in cancer was correlated with prognostic outcomes. However, fibroblasts related study in thyroid cancer remains deficient. Single-cell sequencing data of PTC were analyzed by Seurat R package to explore the ecosystem in PTC and identify fibroblasts cluster. The expression profiles and prognostic values of fibroblast related genes were assessed in TCGA dataset. A fibrosis score model was established for prognosis prediction in thyroid cancer patients. Differentially expressed genes and functional enrichment between high and low fibrosis score groups in TCGA dataset were screened. The correlation of immune cells infiltration and fibrosis score in thyroid cancer patients was explored. Expression levels and prognostic values of key fibroblast related factor were validated in clinical tissues another PTC cohort. Fibroblasts were highly infiltrated in PTC and could interact with other type of cells by single-cell data analysis. 34 fibroblast related terms were differentially expressed in thyroid tumor tissues. COX regression analysis suggested that the constructed fibrosis score model was an independent prognostic predictor for thyroid cancer patients (HR = 5.17, 95%CI 2.31-11.56, P = 6.36E-05). Patients with low fibrosis scores were associated with a significantly better overall survival (OS) than those with high fibrosis scores in TCGA dataset (P = 7.659E-04). Specific immune cells infiltration levels were positively correlated with fibrosis score, including monocytes, M1 macrophages and eosinophils. Our research demonstrated a comprehensive horizon of fibroblasts features in thyroid cancer microenvironment, which may provide potential value for thyroid cancer treatment.

PDZK1 Interacting Protein 1 Promotes the Progression of Papillary Thyroid Cancer.

The incidence of papillary thyroid cancer (PTC) has increased rapidly in recent decades, and tumor progression events are common in PTC. The purpose of our study is to identify the differentially expressed genes (DEGs) correlated with PTC progression and investigate the function of PDZK1IP1 (PDZK1 interacting protein 1) in PTC. We first analyzed DEGs associated with PTC progression between paired PTC and normal thyroid tissues in 3 Gene Expression Omnibus data sets (GSE29265, GSE33630, and GSE60542) and The Cancer Genome Atlas (TCGA) database. Data from the TCGA database and our institution were utilized to explore the relationship between PDZK1IP1 expression and clinicopathological characteristics of PTC. The CCK8 cell proliferation assay, clone formation assay, flow cytometry assay, and the xenograft model were used to investigate the function of PDZK1IP1 in PTC. Thirty-nine DEGs associated with PTC progression were identified, in which only PDZK1IP1 was upregulated in PTC tissue at both messenger RNA and protein levels. In addition, we found that high expression of PDZK1IP1 in the TCGA database was associated with poor progression-free survival, extrathyroidal extension, high stage, tall cell variant, and BRAFV600E mutation of the PTC (P < 0.001). In our collected samples, high expression of PDZK1IP1 was only related to lymph node metastasis (P < 0.05). Overexpression of PDZK1IP1 significantly promoted proliferation and inhibited apoptosis of PTC cells. Knockdown of PDZK1IP1 significantly inhibited proliferation, promoted apoptosis, and prevented xenograft formation of PTC cells. PDZK1IP1 is an oncogene for tumorigenesis and development of PTC and might be a potential therapeutic target.

The Risk Stratification of Papillary Thyroid Cancer With Bethesda Category III (Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance) by Thyroid Fine-Needle Aspiration Could Be Assisted by Tumor Size for Precision Treatment.

PurposeTo investigate the clinical characteristics of papillary thyroid cancer (PTC) classified as Bethesda category III [atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)] by fine-needle aspiration (FNA) for precision treatment.MethodsA total of 1,739 patients diagnosed with Bethesda category III (AUS/FLUS) by FNA were investigated, and 290 patients diagnosed with PTC were analyzed.ResultsThe rate of papillary thyroid microcarcinoma (PTMC) was 82.1% (238/290). The rates of lymph node metastases were 44.9% (22/49) and 25.2% (56/222) for PTC and PTMC, respectively (p = 0.006). The rates of extra-thyroid extension were 46.2% (24/52) and 19.8% (47/237) (p < 0.001). Compared with PTMC, PTC had significantly higher odds ratios (ORs) of 3.41 (1.81–6.44, p < 0.001), 2.19 (1.16–4.13, p = 0.016), and 2.51 (1.29–4.88, p = 0.007) for extra-thyroid extension, multifocality, and lymph node metastases, respectively, after adjustment for age and gender. The larger size and BRAF V600E mutation had a robust synergistic effect for invasive features. The rates of lymph node metastases, multifocality, and extra-thyroid extension were significantly increased with larger sizes harboring BRAF V600E mutation. Compared with PTMC harboring wild type (WT)-BRAF, PTC harboring BRAF V600E mutation had adjusted higher ORs of 3.01 (1.26–8.68, p = 0.015), 3.20 (1.22–8.42, p = 0.018), and 5.62 (2.25–14.01, p < 0.001) for lymph node metastases, multifocality, and extra-thyroid extension, respectively.ConclusionsIn this study, risk stratification was recommended for patients with Bethesda category III (AUS/FLUS) nodules with a size under 1 cm harboring WT-BRAF being regarded as low risk and should be recommended for active surveillance. Nodules with a size over 1 cm harboring WT-BRAF or those under 1 cm harboring BRAF V600E mutation could be regarded as moderate risk, and molecular testing should be recommended. However, those with a size over 1 cm harboring BRAF V600E mutation should be regarded as high risk, and a diagnostic surgery should be recommended.

Vitamin D Receptor Expression and its Clinical Significance in Papillary Thyroid Cancer.

Objective: This study aimed to evaluate the association between vitamin D receptor (an essential component in the vitamin D signaling pathway) and serum vitamin D as well as its clinical significance in papillary thyroid cancer. Methods: This prospective cohort study comprised patients with thyroid tumors who visited our hospital, from 2017 to 2018. The level of vitamin D receptor expression from thyroid tissue was measured in patients with thyroid tumor and evaluated for correlation with serum vitamin D levels and clinicopathologic characteristics of papillary thyroid cancer. Data from 501 patients with papillary thyroid cancer from The Cancer Genome Atlas database were analyzed. Results: Increased vitamin D receptor protein and mRNA expression were observed in papillary thyroid cancer compared to those in normal and benign tissues. Lower vitamin D receptor protein expression was associated with high TNM stage papillary thyroid cancer and low p21 protein expression. Lower relative vitamin D receptor mRNA expression in papillary thyroid cancer was associated with low serum 25-hydroxyvitamin D level. The Cancer Genome Atlas database showed a positive correlation among mRNA expression of vitamin D receptor, CYP24A1, and p21. Conclusions: An association between decreased vitamin D receptor protein expression and advanced stage papillary thyroid cancer, and a correlation between low vitamin D receptor mRNA expression with low serum 25-hydroxyvitamin D level was observed. Low vitamin D receptor expression in papillary thyroid cancer was shown to positively correlate with low serum vitamin D level and disease aggressiveness.