Stage Of Papillary Thyroid Carcinoma Research Articles

Association of Lymph Nodes Positive Rate With the Risk of Recurrence in Patients With Stage T1 Papillary Thyroid Cancer.

The incidence of lymph node metastasis in papillary thyroid carcinoma (PTC) is common and a significant risk factor for local recurrence; however, its impact on recurrence patterns among low-risk patients remains uncertain. We aimed to elucidate the effect of metastatic lymph node on recurrence type. The medical records of 1209 patients with stage T1 PTC who underwent unilateral thyroidectomy with ipsilateral central lymph node dissection were retrospectively analyzed. The study first identified risk factors for different types of recurrence and then categorized patients as high or low risk based on their lymph node positive ratio (LNPR). The diagnostic accuracy of LNPR in predicting recurrence was compared using receiver operating characteristic (ROC) curve analysis, while differences in recurrence-free survival were assessed using the Kaplan-Meier method. During follow-up, a total of 502 (41.5%) patients had central lymph node metastasis and 52 (4.3%) patients experienced recurrence. Notably, LNPR was significantly higher in relapsed patients compared to nonrelapsed patients, with mean values of 0.45 and 0.23, respectively (P < .001). The recurrence rate of residual thyroid did not differ significantly across different T stages (P = .679), N stages (P = .415), or LNPR risk groups (P = .175). However, the recurrence rate of lymph nodes showed a significant correlation with LNPR (P < .001). The area under the ROC curves for LNPR risk stratification at 5 and 10 years were approximately 0.691 and 0.634, respectively, both of which outperformed N stage. The findings underscore the significance of LNPR's reliability as a prognostic indicator for local lymph node recurrence in patients diagnosed with T1 stage PTC.

Risk factors for lateral lymph node metastasis in T1 stage papillary thyroid carcinoma.

Risk factors for lateral lymph node metastasis in T1 stage papillary thyroid carcinoma.

Analysis of risk factors for lateral lymph node metastasis in T1 stage papillary thyroid carcinoma: a retrospective cohort study.

The occurrence of cervical lymph node metastasis in T1 stage papillary thyroid carcinoma (PTC) is frequently observed. Notably, lateral lymph node metastasis (LLNM) emerges as a critical risk factor adversely affecting prognostic outcomes in PTC. The primary aim of this investigation was to delineate the risk factors associated with LLNM in the initial stages of PTC. This retrospective analysis encompassed 3,332 patients diagnosed with T1 stage PTC without evident LLNM at the time of diagnosis. These individuals underwent primary surgical intervention at West China Hospital, Sichuan University between June 2017 and February 2023. The cohort was divided into two groups: patients manifesting LLNM and those without metastasis at the time of surgery. Additionally, T1 stage PTC patients were subdivided into T1a and T1b categories. Factors influencing LLNM were scrutinized through both univariate and multivariate analyses. The incidence of LLNM was observed in 6.2% of the cohort (206 out of 3,332 patients). Univariate analysis revealed significant correlations between LLNM and male gender (P<0.001), tumor localization in the upper lobe (P<0.001), maximal volume of the primary tumor (P<0.001), largest tumor diameter (P<0.001), multifocality (P<0.001), and bilaterality (P<0.001), with the exception of age (P=0.788) and duration of active surveillance (AS) (P=0.978). Multivariate logistic regression analysis identified male gender (P<0.001), upper lobe tumor location (P<0.001), maximal primary tumor volume (P<0.001), and multifocality (P<0.001) as independent predictors of LLNM. However, age categories (≤55, >55 years), maximum tumor diameter, bilaterality, and surveillance duration did not exhibit a significant impact. Comparative analyses between T1a and T1b subgroups showed congruent univariate results but revealed differences in multivariate outcomes. In the T1a subgroup, gender, tumor location, and multifocality (all P<0.05) were associated with elevated LLNM risk. Conversely, in the T1b subgroup, tumor location, dimensions, and multifocality (all P<0.05) were significant predictors of LLNM risk, whereas gender (P=0.097) exerted a marginal influence. The investigation highlights several key risk factors for LLNM in T1 stage PTC patients, including gender, upper lobe tumor location, larger tumor size, and multifocality. Conversely, prolonged AS and younger age did not significantly elevate LLNM risk, suggesting the viability of AS as a strategic option in selected cases.

Transoral and submental endoscopic thyroidectomy (TOaST) for early stage papillary thyroid carcinoma: a real-world data retrospective cohort study.

Although transoral endoscopic thyroidectomy (TOETVA) is widely utilized in clinical practice, some problems and restrictions still remain. Our study compared the perioperative features and early surgical efficacy of TOETVA and a modified transoral and submental endoscopic thyroidectomy (TOaST) in early stage papillary thyroid carcinoma (PTC). The clinical data of PTC patients who underwent endoscopic thyroidectomy, including 42 modified TOaST patients and 114 traditional TOETVA patients, were retrospectively collected. Propensity score matching was employed to reduce patient selection bias. The perioperative features and early surgical efficacy data of two groups were compared. The operation time of the TOaST group was significantly shorter than that of the TOETVA group (150.00 ± 35.47min vs. 168.75 ± 44.49min; P = 0.030). Furthermore, the TOaST group required shorter days fora normal diet (3.38 ± 0.93days vs. 4.04 ± 1.03days; P = 0.000) and a shorter hospital stay than the TOETVA group (5.85 ± 2.17days vs. 6.12 ± 2.01days; P = 0.003). There was no statistical difference in complications between the two groups, but the probability of numbness of the lower lip and chin in the TOaST group was lower than that in the TOETVA group(5.12% vs. 13.04%, P = 0.321). The symptoms of mandibular numbness and hoarseness of most patients were relieved in both groups 6months after surgery, and no abnormalities and recurrence were found in the thyroid ultrasound. All the patients were satisfied with the appearance of their surgical incision. In early stage PTC patients, TOaST had the same surgical effectiveness as traditional TOETVA but can minimize the probability of mandibular numbness and improve the perioperative quality of life.

AIUM Practice Parameter for the Performance and Interpretation of Diagnostic Ultrasound of the Thyroid and Extracranial Head and Neck.

AIUM Practice Parameter for the Performance and Interpretation of Diagnostic Ultrasound of the Thyroid and Extracranial Head and Neck.

Evolution of intra-tumoral heterogeneity across different pathological stages in papillary thyroid carcinoma

BackgroundIntra-tumor heterogeneity (ITH) results from the continuous accumulation of mutations during disease progression, thus impacting patients’ clinical outcome. How the ITH evolves across papillary thyroid carcinoma (PTC) different tumor stages is lacking.MethodsWe used the whole-exome sequencing data from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) cohort to track the ITH and assessed its relationship with clinical features through different stages of the PTC progression. We further assayed the expression levels of the specific genes in papillary thyroid cancer cell lines compared to an immortalized normal thyroid epithelial cell line by qRT-PCR.ResultsWe revealed the timing of mutational processes and the dynamics of the temporal acquisition of somatic events during the lifetime of the PTC. ITH significantly influences the PTC patient’s survival rate and, as genetic heterogeneity increases, the prognosis gets worse in advanced tumor stages. ITH also affects the mutational architecture of each clinical stage which is subject to periodic fluctuations. Different mutational processes may cooperate to shape a stage-specific mutational spectrum during the progression from early to advanced tumor stages. Moreover, different evolutionary paths characterize PTC progression across pathological stages due to both mutations recurrently occurring in all stages in hotspot positions and distinct codon changes dominating in different stages. A different expression level of specific genes also exists in different thyroid cancer cell lines.ConclusionsOur findings suggest ITH as a potential unfavorable prognostic factor in PTC and highlight the dynamic changes in different clinical stages of PTC, providing some clues for the precision medicine and suggesting different diagnostic decisions depending on the clinical stages of patients. Finally, complete clear guidelines to define risk stratification of PTC patients are lacking; thus, this work could contribute to defining patients who need more aggressive treatments and, in turn, could reduce the social burden of this cancer.

Analysis of Risk Factors Associated With Central Lymph Node Metastasis in Papillary Thyroid Carcinoma With cT1N0 Stage.

AimAnnual T1 stage papillary thyroid carcinoma (PTC) incidence rates continue to rise, yet the optimal treatment for this cancer type remains controversial. Central lymph node metastasis (CLNM) is a critical determinant in the context of treatment decision-making. While several prior studies have evaluated patients with clinica l T1a(cT1a) stage PTC, there have been fewer analyses of clinical T1b(cT1b) disease to date. The present study was thus formulated to explore predictors of CLNM in patients with cT1a and cT1b stage PTC.MethodsA retrospective analysis of data including clinicopathological characteristics and BRAFV600E mutation status was conducted for 452 PTC patients undergoing surgical treatment. Logistic univariate and multivariate analyses were performed to identify risk factors associated with CLNM in particular patients’ characteristics and the accuracy of the established logistic regression models was evaluated using the R software platform.ResultsRespective CLNM incidence rates in cT1a and cT1b disease were 39.39% and 67.21%. Factors associated with a higher risk of CLNM among PTC(cT1a) patients included male sex, young age, tumor size, contact with capsule, and multifocality as determined through comparisons of the area under the curve for logistic regression models. Whereas male sex and age were associated with CLNM risk in PTC(cT1b) patients in univariate and multivariate analyses, age was the only risk factor associated with CLNM incidence among women with PTC(cT1b).ConclusionPredictors of CLNM differ between PTC patients with cT1a and cT1b stage disease, and a comprehensive assessment of these risk factors should thus be conducted when designing individualized treatment regimens for PTC patients.

Benign and malignant thyroid nodules with autoimmune thyroiditis.

The prevalence of autoimmune thyroiditis (AT) in papillary thyroid carcinoma (PTC) is still controversial. The aim of this study was to investigate the frequency of coexistence of PTC with AT versus that of the coexistence of benign nodules with AT. This was a cross-sectional retrospective study including patients operated on for thyroid nodules from January 2011, to April 2021. The frequency of papillary carcinomas cooccurring with AT was compared to that of benign nodules cooccurring with AT, which was assessed based on cytopathological diagnosis after thyroidectomy. The study included 668 cases of benign nodules and 420 cases with PTC. No statistically significant difference was observed between cases of benign and PTC nodules regarding the presence of AT (25% vs. 28%, respectively, p = 0.177). The size of the PTC compared to that of the benign predominant nodules was significantly smaller both in the absence (0.96 ± 1.09 cm vs. 2.19 ± 1.06 cm, p < 0.05) and in the presence (0.77 ± 0.76 cm vs. 1.67 ± 1.08 cm, p < 0.01) of AT. In the binary logistic regression analysis of the PTC, the only variable associated with AT was multifocality (odds ratio: 1.750, 95% confidence intervals: 1.131-2.706, p = 0.013). The incidences of lymph node involvement and advanced stage PTC were very low both in the presence and absence of AT. The nodules present with PTC were not more likely to coexist with AT than benign nodules were. The small incidence of advanced PTC indicates a significant improvement in early-stage diagnosis.

Bioinformatics analysis of downstream circRNAs and miRNAs regulated by Runt-related transcription factor 1 in papillary thyroid carcinoma.

This study sought to clarify the role of Runt-related transcription factor 1's (RUNX1's) regulation of downstream circular ribonucleic acid (circRNA) in the occurrence and development of papillary thyroid carcinoma (PTC) and to explore its mechanism of action. The levels of RUNX1 were analyzed in PTC tumor tissues and adjacent non-tumor tissues in different types and at different stages via reverse-transcription quantitative polymerase chain reaction (RT-qPCR). The expression pattern and functional role of RUNX1 were analyzed in PTC cells via RT-qPCR, Western blotting, and Transwell assays. This study explored the differential expression of circRNA and microRNA (miRNA) in cells after knocking down RUNX1 through high-throughput sequencing and examined the changes in downstream signaling pathways through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RUNX1 was upregulated in PTC tissues, and the expression levels of RUNX1 were related to PTC stage. The knockdown of RUNX1 inhibited the proliferation, migration, and invasion of cells. The high-throughput sequencing results showed that after RUNX1 knockdown, 29 circRNAs (11 upregulated and 18 downregulated) and 20 miRNAs (8 upregulated and 12 downregulated) had the most significant differential expression. The GO analysis of the differential circRNA downstream genes showed that the iron channel-related pathways, endosomal transport, learning, and memory pathways had the largest number of differential genes, and the most significant changes. The KEGG analysis showed that there were 2 pathways with P values <0.05; that is, the glycosaminoglycan synthesis and transcription dysregulation pathways. The GO analysis of the differential miRNA downstream genes showed that the protein binding and cytoplasmic pathways had the largest number of differential genes and the greatest level of difference. The KEGG analysis showed that the tumor-related pathways, phosphatidylinositol-3-kinase and protein kinase B, glycoprotein, cytoskeleton, Ras, and Rap1 pathways changed the most significantly. RUNX1 is highly expressed in PTC. We conducted high-throughput sequencing to analyze the effect of knocking down RUNX1 on the levels of circRNA and miRNA in PTC. The GO and KEGG analyses revealed that the iron channel-related pathways, endosomal transport, learning and memory, glycosaminoglycan synthesis, and transcriptional disorder-related signaling pathways were enriched.

Expression and correlation of cycde-2 protein and nuclear factor kB in serum of patients with papillary thyroid carcinoma

To determine the clinical prediction role of the serum level of cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) in papillary thyroid carcinoma (PTC) patients. 60 cases of PTC from February 2015 to May 2017 were collected to perform retrospective analysis and 10 patients with normal thyroid function were included as control group. We detected two immune factors: COX-2 and NF-κB in serum and analyse its relation to disease-free survival, overall survival, clinicopathological of PTC. COX-2 expression was associated with tumor tissue grade (p = 0.029), which was more abundant in III or IV stage (p = 0.087) patients. Relative to control group, PTC patients exhibited low NF-κB level. Survival analysis showed that the total survival time and disease-free survival time of low NF-κB level was shorter than that of control group (p < 0.05). Low COX-2 expression was associated with highly differentiated tumors (p = 0.015). However, COX-2 expression exerted little link with tumor grade, type, recurrent, age and clinical stage of PTC (p > 0.05).Further, regression analysis showed COX-2 and NF-κB expression is a risk factor for PTC, affecting prognosis. PTC patients exhibited low COX-2 and NF-κB expression, proving to correlate with the PTC development.

Calcification and Expression of Bone Morphogenetic Protein-4 in Papillary Thyroid Carcinoma

Background/Aim: The purpose of this study was to investigate whether bone morphogenetic protein (BMP)-4 expression differs according to the presence of calcification in papillary thyroid carcinoma and to investigate if calcification and BMP-4 expression are associated with metastasis of papillary carcinoma.Methods: We performed the study using paraffin-embedded tissues of 55 patients who underwent thyroidectomy in Kosin University Gospel Hospital. Of those 55 cases, 36 were papillary thyroid carcinomas, and 19 were benign tumors. Immunohistochemical staining with BMP4 antibody was performed on the paraffin-embedded tissues.Results: Among the 36 papillary thyroid carcinomas, 20 (55.6%) of extrathyroidal invasion and 21 (58.3%) of lymph node metastasis were observed. The presence of calcification was significantly different according to incidence of extranodal invasion (p = 0.02), lymphovascular invasion (p &lt; 0.001), and lymph node metastasis (p = 0.04). BMP-4 expression was weakly positive in benign tumors and strongly positive in papillary thyroid carcinoma (p &lt; 0.001). BMP-4 expression was significantly different by TNM stage (p &lt; 0.001).Conclusion: In the present study, the presence of calcification in thyroid papillary carcinoma was associated with tumor metastasis. BMP-4 was strongly expressed in papillary thyroid carcinoma and was associated with the stage of papillary thyroid carcinoma.

CircRNA NRIP1 promotes papillary thyroid carcinoma progression by sponging mir-195-5p and modulating the P38 MAPK and JAK/STAT pathways

BackgroundCircular RNAs (circRNAs) have become a hot topic in the area of tumor biology due to its closed structure and the post-transcriptional regulatory effect. This study aims to clarify the roles of circRNA nuclear receptor-interacting protein 1 (NRIP1; circNRIP1) and the possible mechanisms in papillary thyroid carcinoma (PTC).MethodsThe real-time PCR was used to detect the expression level of CircRNA NRIP1 in PTC specimens and cell lines. The effects of CircRNA NRIP1 and miR-195-5p on the PTC cell functions were detected by MTT, transwell, and flow cytometry assays. Dual-luciferase reporter assays and pull down assays were used to verify the association between circRNA NRIP1 and miR-195-5p. The murine xenograft models were constructed to detect the roles of CircRNA NRIP1 and miR-195-5p. Western blot was applied to detect the effects of CircRNA NRIP1 and miR-195-5p on the P38 MAPK and JAK/STAT singling pathways.ResultsCircRNA NRIP1 was over-expressed in PTC tissues and cells and the high levels of CircRNA NRIP1 were correlated with advanced PTC stage. Depletion of CircRNA NRIP1 inhibited PTC cell proliferation, invasion, while accelerated apoptosis. miR-195-5p upregulation repressed proliferation and invasion capabilities, and accelerated apoptosis of PTC cell lines and restraining the growth of tumor xenografts, while the functions were reversed following CircRNA NRIP1 overexpression in PTC cells and tumor xenografts. Besides, the protein levels of p-p38, p-JAK2 and p-STAT1 were remarkably down-regulated in miR-195-5p overexpressed PTC cells and tumor xenografts, whereas CircRNA NRIP1 up-regulation overturned the impacts.ConclusionsIn conclusion, CircRNA NRIP1 promoted PTC progression by accelerating PTC cells proliferation, invasion and tumor growth, while impeding apoptosis by way of sponging miR-195-5p and regulating the P38 MAPK and JAK/STAT pathways.

Characterization of Graves' disease development after partial thyroidectomy for thyroid cancer.

BackgroundGraves’ disease (GD) is the most common cause of hyperthyroidism, and it rarely develops in patients who undergo partial thyroid removal for thyroid cancer. The present study characterized and analyzed the GD development mechanism after partial thyroidectomy for thyroid cancer and suggested optimized treatments for the condition.MethodsA retrospective study from January 2013 to March 2017 was conducted in patients where GD occurred after partial thyroidectomy for thyroid cancer. Reviewed laboratory data included free 3,5,3'-triiodothyronine, free thyroxine, thyroid-stimulating hormone (TSH), thyroglobulin (Tg), anti-Tg antibody, anti-peroxidase antibody, and TSH receptor antibody levels. All laboratory indicators included preoperative and postoperative data. In addition, we collected patient neck ultrasound examination records and radioiodine (RAI) uptake test data.ResultsAmong 5,600 patients diagnosed with GD, 5 (0.09%) met the inclusion criteria and were enrolled. Patient mean age was 47.4±9.6 years, and all were female with a papillary thyroid carcinoma stage I diagnosis. The interval between partial thyroidectomy and hyperthyroidism onset ranged from 2 to 25 months. We proposed possible mechanisms for this medical condition and identified several factors accelerating the disease course. To treat GD, a low RAI (30 mCi) dose was prescribed to patients. All exhibited hypothyroidism at a 3- or 6-month follow-up, with stable clinical status at 1-year follow-up.ConclusionsGD rarely develops after partial thyroidectomy for thyroid cancer. We recommend a low RAI dose to manage GD and ablate the remnants of thyroid cancer.

Large contribution of copy number alterations in early stage of Papillary Thyroid Carcinoma

Papillary Thyroid Carcinoma (PTC) accounts for approximately 85% of patients with thyroid cancer. Despite its indolent nature, progression to higher stages is expected in a subgroup of patients. Hence, genomic characterization of the early stages of PTC may help to identify this subgroup, leading to better clinical management.Here, we conducted a comprehensive mutational and somatic copy number alteration (SCNA) investigation on 277 stage one PTC from TCGA.SCNA analysis revealed amplification and deletion of several cancer related genes. We found amplification of 60 oncogenes (Oncs), from which 15 were recurrently observed. Deletion of 58 tumor suppressors (TSs) was also detected. MAPK, PI3K-Akt, Rap1 and Ras were the signaling pathways with large numbers of amplified Oncs. On the other hand, deleted TSs belonged mostly to cell cycle, PI3K-Akt, mTOR and cellular senescence pathways. This suggests that despite heterogeneity in SCNA events, the final results would be the activation/deactivation of a few cancer signaling pathways. Of note, despite large amounts of heterogeneity in stage one PTC, recurrent broad deletion on Chr22 was detected in 21 individuals, leading to deletion of several tumor suppressors.In parallel, the oncogenic/pathogenic mutations in the RTK-RAS and PI3k-Akt pathways were detected. However, no pathogenic mutation was identified in known tumor suppressor genes. In order to identify a potential subgroup of BRAF (V600E) positive patients, who might progress to higher stages, low frequency mutations accompanying BRAF (V600E) were also identified.In conclusion, our findings imply that SCNA have a substantial contribution to early stages of PTC. Experimental validation of the observed genomic alterations could help to stratify patients at the time of diagnosis, and to move toward precision medicine in PTC.

Differences in Clinicopathological Characteristics of Papillary Thyroid Carcinoma between Symptomatic and Asymptomatic Patients with Primary Hyperparathyroidism.

Background Popularization of cervical ultrasound led to higher detection of papillary thyroid carcinoma (PTC) and primary hyperparathyroidism (PHPT), as well as increasing percentage of asymptomatic PHPT in China. Although the coexistence of PTC and PHPT has been reported, it is unknown whether the clinicopathological features of PTC differ between asymptomatic and symptomatic PHPT patients. Methods We retrospectively reviewed the medical records of 304 PHPT patients treated in our hospital between January 2009 and July 2020, including 217 females and 87 males with the average age of 53.27 ± 13.54 years. Of the 304 patients, 181 were symptomatic PHPT patients and 123 were asymptomatic PHPT patients. We analyzed the laboratory results, postoperative pathology, and the TNM stage of PTC between asymptomatic and symptomatic PHPT patients. Results Concurrent thyroid nodules were found in 61.51% of PHPT patients, and the prevalence of PTC in thyroidectomized PHPT patients was 29.89% in our cohort. Lower serum parathyroid hormone (PTH) (p < 0.05) and calcium (p < 0.05) were found in PHPT patients with PTC compared to patients with benign thyroid lesion. Compared with the symptomatic PHPT patients, the asymptomatic PHPT patients showed lower serum calcium (p < 0.05), serum chlorine (p < 0.05), alkaline phosphatase (p < 0.05), PTH (p < 0.05), and bone turnover markers (p < 0.05) but higher prevalence of thyroid nodules (70.73% versus 55.24%, p < 0.05) and PTC (15.44% versus 3.87%, p < 0.05). All the PTC in symptomatic PHPT patients were papillary microcarcinoma limited to the thyroid, while 68.42% and 15.78% of the PTC in asymptomatic PHPT patients showed microscopic extrathyroidal extension and lymph node metastases, respectively. Moreover, 36.84% (7/19) of the PTC patients in asymptomatic group showed multifocality, which was much higher than 14.29% (1/7) in the symptomatic group; however, no statistical significance was found (p=0.24). Conclusions The concomitant PTC in asymptomatic PHPT patients showed a higher rate of microscopic extrathyroidal invasion when compared to symptomatic PHPT patients. So the FNA is essential to the asymptomatic PHPT patients with suspicious thyroid nodules and once the PTC is confirmed, concurrent parathyroidectomy should be performed with thyroidectomy in asymptomatic PHPT patients.

Higher EU-TIRADS-Score Correlated with BRAF V600E Positivity in the Early Stage of Papillary Thyroid Carcinoma.

The data demonstrating a correlation between sonographic markers of malignancy of thyroid cancer (TC) and its genetic status are scarce. This study aimed to assess whether the addition of genetic analysis at the preoperative step of TC patients’ stratification could aid their clinical management. The material consisted of formalin-fixed paraffin-embedded tumor fragments of 49 patients who underwent thyroidectomy during the early stages of papillary TC (PTC). Tumor DNA and RNA were subjected to next-generation sequencing (NGS) on Ion Proton using the Oncomine™ Comprehensive Assay panel. We observed a significant correlation between BRAF V600E and a higher EU-TIRADS score (p-value = 0.02) with a correlation between hypoechogenicity and taller-than-wide tumor shape in analysed patients. There were no other significant associations between the identified genetic variants and other clinicopathological features. For TC patient’s stratification, a strong suspicion of BRAF V600E negativity in preoperative management of TC patients could limit the over-treatment of asymptomatic, very low-risk, indolent disease and leave room for active surveillance.

Analyze and compare the predictors of ipsilateral central lymph node metastasis in papillary thyroid carcinoma with cT1a and cT1b stage

Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). The aim of this study was to compare the cT1a and cT1b stages of PTC and to analyze the predictive factors of ipsilateral central lymph node metastasis (CLNM). In total, 212 PTC (cT1N0) patients underwent hemi-thyroidectomy with ipsilateral central lymph node dissection (CLND) between 2019 and 2020 in our hospital. Univariate and multivariate analyses identified the predictive factors for CLNM of PTC (cT1aN0 and cT1bN0), and compared the differences between the two stages. The total rate of ipsilateral CLNM was 31.13% (66/212), and the ipsilateral CLNM rate in cT1b stage was higher than that in cT1a stage (48.84% vs. 26.63%), with significant differences (p=0.005). cT1b stage was more prone to capsule invasion than cT1a stage (41.86% vs. 2.37%), with significant differences (p‹0.001). The multivariate analysis showed that tumor size (n>5mm) was an independent predictive factor for CLNM in cT1a stage (p=0.002), with an odds ratio (OR) of 0.228 (95% confidence interval (95% CI): 0.079-0.655). Capsular invasion (p=0.048) and tumors located in the middle and lower parts (p=0.022) were independent predictive factors for CLNM in cT1b stage, with ORs of 0.157 (95% CI: 0.034-0.724) and 0.075 (95% CI: 0.007-0.847), respectively. The rate of CLNM increases with increase of tumor size. Patients in cT1b stage are more prone to capsule invasion and CLNM. For the cT1b stage of PTC, predictive factors should be correctly evaluated to guide surgical treatment for PTC patients.

Identification of key genes of papillary thyroid carcinoma by integrated bioinformatics analysis.

Background: Papillary thyroid carcinoma (PTC) is one of the fastest-growing malignant tumor types of thyroid cancer. Therefore, identifying the interaction of genes in PTC is crucial for elucidating its pathogenesis and finding more specific molecular biomarkers.Methods: Four pairs of PTC tissues and adjacent tissues were sequenced using RNA-Seq, and 3745 differentially expressed genes were screened (P<0.05, |logFC|>1). The enrichment analysis indicated that the vast majority of differentially expressed genes (DEGs) may play a positive role in the development of cancer. Then, the significant modules were analyzed using Cytoscape software in the protein–protein interaction network. Survival analysis, TNM analysis, and immune infiltration analysis of key genes were analyzed. And the expression of ADORA1, APOE, and LPAR5 genes were verified by qPCR in PTC compared with matching adjacent tissues.Results: Twenty-five genes were identified as hub genes with nodes greater than 10. The expression of 25 genes were verified by the GEPIA database, and the overall survival and disease-free survival analyses were conducted with Kaplan–Meier plotter. We found only three genes were confirmed with our validation and were statistically significant in PTC, namely ADORA1, APOE, and LPAR5. Further analysis found that the mRNA levels and methylation degree of these three genes were significantly correlated with the TNM staging of PTC. And these three genes were related to PTC immune infiltration. Verification of the expression of these three genes by RT-qPCR and Western blot further confirmed the reliability of our results.Conclusion: Our study identified three genes that may play key regulatory roles in the development, metastasis, and immune infiltration of papillary thyroid carcinoma.

Mutations of the TERT promoter are associated with aggressiveness and recurrence/distant metastasis of papillary thyroid carcinoma.

Several previous studies have shown that mutations in B-Raf proto-oncogene (BRAF) and telomerase reverse transcriptase (TERT) can be used for the diagnosis and prognosis of papillary thyroid carcinoma (PTC). However, whether mutations in BRAF and the TERT promoter may improve the accurate identification and risk stratification of high-risk patients in the early stage of PTC remains unclear and requires further investigation. In the present study, mutations in BRAF and the TERT promoter were examined in 205 patients using PCR and Sanger DNA sequencing. The potential association between mutations in these two genes and the clinicopathological characteristics of patients with PTC was then analyzed. BRAF mutations were identified in 169/205 (82.4%) patients, whereas only 8/205 (3.9%) patients presented mutations in the TERT promoter, seven patients exhibited a C228T mutation, and the remaining one had a C250T mutation. There were 6/205 (2.9%) patients with mutations in both BRAF and the TERT promoter. Importantly, compared with patients with no mutations, patients with mutations in BRAF were more likely to exhibit mutations in the TERT promoter. A significant difference in lymph node metastasis was found between the BRAF V600E mutation group and the group without mutations in BRAF. Mutations in the TERT promoter were significantly correlated with older age, extrathyroidal invasion, tumor multifocality and advanced tumor/node/metastasis stage, which are associated with the aggressiveness of PTC. Moreover, compared with patients exhibiting mutations in BRAF, mutations in the TERT promoter were found to be significantly associated with aggressive clinicopathological features and higher risk of recurrence or distant metastasis. Collectively, mutations in the TERT promoter were not frequent, but were significantly correlated with more aggressive clinicopathological features of PTC. Therefore, mutations in the TERT promoter may be an important factor in the genetic background of PTC, and detection of such mutations may help the accurate identification and management of high-risk patients with recurrent or distant metastasis.

LncRNA GAS8-AS1 genetic alterations in papillary thyroid carcinoma and their clinical significance.

The long non-coding RNA (lncRNA) GAS8-AS1 is the second-most frequently altered gene, following the BRAF gene, in papillary thyroid carcinoma (PTC). We aimed to study the specificity and significance of genetic alterations in GAS8-AS1 in PTC. In this study, we reported the prevalence of genetic alterations of GAS8-AS1 in tissues of 48 nodular goiter, 573 papillary thyroid cancer, 95 colorectal cancer, 101 non-small cell lung cancer, 92 glioma, and 69 gastrointestinal stromal tumor patients, and in peripheral white blood cells of 286 healthy volunteers. We observed that the genomic sequence of GAS8-AS1 had a high frequency of genetic alterations in addition to the previously reported c.713A>G/714T>C substitution. Substitution of c.713A>G was completely linked with four other loci at c.714T>C, c.728A>G, c.737G>A, and c.752G>A. Two novel substitutions at c.749G>A and c.826A>G were also found. Interestingly, evidence from different samples indicated that these variations were not unique variants for PTC; they were also found in other malignant tissues and white blood cells of healthy volunteers. The c.713A>G substitution was associated with the T stage of PTC, while c.749G>A was more likely to occur in younger patients with PTC. PTC patients carrying heterozygous variants at the c.749 and c.826 loci had a higher risk of developing multiple lesions. These associations were also observed in patients with PTC and concomitant benign thyroid disease. Notably, the rare homozygous GG at the c.826 site conferred a higher risk of developing T2 PTC without benign thyroid disease, and a lower risk of developing T2 PTC with benign thyroid disease. Alterations of c.749G>A and c.826A>G had higher levels of serum TSH (thyroid stimulating hormone) in PTC subjects. Our study provides evidence that the detection of GAS8-AS1 genetic alterations would be useful in diagnostic screening and prognostic assessment of PTC.