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Thyroid cancer is the endocrine tumor with the highest incidence at present. It originates from the thyroid follicular epithelium or follicular paraepithelial cells. There is an increasing incidence of thyroid cancer all over the world. We found that SRPX2 expression level was higher in papillary thyroid tumors than in normal thyroid tissues, and SRPX2 expression was closely related to tumor grade and clinical prognosis. Previous reports showed that SRPX2 could function by activating PI3K/AKT signaling pathway. In addition, in vitro experiments showed that SRPX2 promoted the proliferation and migration of papillary thyroid cancer (PTC). In conclusion, SRPX2 could promote the malignant development of PTC. This may be a potential treatment target for PTC., (© 2023. The Author(s).)

Thyroid cancer is the most prevalent endocrine tumor and its incidence is fast-growing worldwide in recent years. Differentiated thyroid cancer (DTC) is the most common pathological subtype which is typically curable with surgery and Radioactive iodine (RAI) therapy (approximately 85%). Radioactive iodine is the first-line treatment for patients with metastatic Papillary Thyroid Cancer (PTC). However, 60% of patients with aggressive metastasis DTC developed resistance to RAI treatment and had a poor overall prognosis. The molecular mechanisms of RAI resistance include gene mutation and fusion, failure to transport RAI into the DTC cells, and interference with the tumor microenvironment (TME). However, it is unclear whether the above are the main drivers of the inability of patients with DTC to benefit from iodine therapy. With the development of new biological technologies, strategies that bolster RAI function include TKI-targeted therapy, DTC cell redifferentiation, and improved drug delivery via extracellular vesicles (EVs) have emerged. Despite some promising data and early success, overall survival was not prolonged in the majority of patients, and the disease continued to progress. It is still necessary to understand the genetic landscape and signaling pathways leading to iodine resistance and enhance the effectiveness and safety of the RAI sensitization approach. This review will summarize the mechanisms of RAI resistance, predictive biomarkers of RAI resistance, and the current RAI sensitization strategies., Competing Interests: Conflict of interest The authors declare no competing interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Although papillary thyroid cancer (PTC) has a low mortality rate, the rate of recurrence remains relatively high. This study aims to develop a molecular signature to predict the recurrence of PTC., Methods: A total of 333 PTC patients' data from The Cancer Genome Atlas (TCGA) were included. We calculated tumor mutation burden (TMB) and analyzed the mutation status of BRAF and TERT promoter., Results: Tumor recurrence occurred in 17 of 263 cases in TMB-L patients versus 14 of 70 cases in TMB-H patients (hazard ratio [HR], 3.55; 95% confidence interval [CI], 1.75-7.21; P < 0.001). The HR for recurrence in TMB-H patients remained significant after adjustment for classical clinicopathologic factors (patient age, gender, extrathyroidal extension and lymph node metastasis). These clinical factors had no effect on recurrence rate in TMB-L patients, but had a strong adverse effect on the prognosis of TMB-H patients. Compared with TMB-L patients lacking mutation, the HR (95% CI) of recurrence for TMB-H patients with coexisting BRAF V600E and/or TERT C228/250 T mutations was 6.68 (2.41-18.57), which remained significant after adjustment for clinicopathological factors. The mutation status of BRAF V600E and TERT C228/250 T had little effect on PTC recurrence in TMB-L patients. Either of the mutation was associated with high recurrence rate in TMB-H patients., Conclusions: The presence of BRAF V600E and/or TERT promoter mutations denotes a high risk of recurrence in TMB-H patients. This represents a powerful molecular prognostic genotype that can help predict patients with the highest risk of recurrence., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Whole transcriptome analysis was conducted to identify differentially expressed RNAs and regulatory networks associated with papillary thyroid carcinoma (PTC)., Methods: A weighted gene co-expression network analysis based on high-throughput sequencing data for six pairs of PTC and adjacent tissue samples was conducted to understand the biological functions and regulatory networks involving long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs)., Results: We detected 131, 338, 31, and 556 differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs, respectively. We identified modules that were significantly positively and negatively related to cancer and lymph node metastasis. Gray and turquoise modules were positively correlated with cancer phenotypes (p < 0.05), whereas yellow, brown, and blue modules were negatively correlated with cancer (p < 0.05). Gray module was positively correlated with lateral lymph node metastasis (p = 0.02). Kaplan-Meier analyses revealed that the levels of transmembrane protein 63C (TMEM63C), lysyl oxidase-like 1 (LOXL1), collagen type V alpha 1 chain (COL5A1), ADAM metalloproteinase with thrombospondin type I motif 2 (ADAMTS2), and LysM-domain containing 3 (LYSMD3) were significantly associated with overall survival (p < 0.05). Significant increase in the expression of COL5A1 and LOXL1 in tumor tissues was validated by quantitative real-time polymerase chain reaction (p < 0.05). COL5A1 and LOXL1 promoted PTC cell growth and invasion in vitro., Conclusions: We identified COL5A1 and LOXL1 as potential prognostic biomarkers, providing new insights into the occurrence and progression of PTC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

This study aimed to compare the surgical safety and outcomes of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and gasless endoscopic thyroidectomy transaxillary approach (GETTA). This retrospective study assessed 150 patients managed with the TOETVA at the Yantai Yuhuangding hospital and 150 patients managed via the GETTA at the Zhenjiang Provincial People's Hospital. The procedures were compared in terms of workspace creation time, operating time, complications, post-operative complaints, cosmetic satisfaction, and the efficacy of central neck lymph-node dissection. There was no significant between-group difference in terms of post-operative complications. The average workspace creation and operating times were significantly shorter for GETTA than for TOETVA (P values for both < 0.001). The average number of lymph nodes dissected from the central compartment of the neck was higher in the TOETVA group than in the GETTA group (7.2 ± 4.6 vs. 3.9 ± 3.0, P < 0.001). The mean swallowing impairment index-6 scores at 1 month were significantly lower in the GETTA group than in the TOETVA group (1.5 ± 1.2 vs 2.6 ± 1.4, P < 0.001). Over 97% of all patients (both groups) were either satisfied or very satisfied with the cervical cosmetic outcomes at 3 months post-surgery (P = 0.099). TOETVA and GETTA are both safe procedures with good cervical cosmetic outcomes for well-selected patients. Although TOETVA is more efficacious in terms of central lymph nodes dissection, GETTA has a greater time-cost advantage., (© 2021. Italian Society of Surgery (SIC).)

Context: Malignant thyroid tumor with distant metastasis is associated with poor outcome. Early detection of distant metastasis is of great clinical importance., Objective: Thyroid tumor infiltrated with T cells can serve as a biomarker for monitoring metastasis., Design: A retrospective analysis was performed of patient clinical samples collected between 2012 to 2018, using T-cell receptor sequencing (TCR-seq) for clinical exploration., Setting: This study took place at Zhejiang Cancer Hospital., Patients: Sixty-eight patients with papillary thyroid cancer (PTC) (distinct metastatic status) and 21 patients with benign nodules were enrolled. All patients had not received any treatment before surgery., Main Outcome Measure: The characteristics of TCRβ complementary-determining region 3 (CDR3) for each patient were determined by high-throughput sequencing., Results: The TCRβ diversity of malignant tumors is significantly higher than benign nodules both in blood and tumor samples (Shannon index, blood, P < .01; tumor, P < .001). The malignant tumors with distant metastasis or invasiveness showed lower TCRβ diversity than nonmetastasis (Shannon index, P < .01) or noninvasive (Shannon index, P < .01) malignant tumors. Analysis of the Morisita-Horn similarity index indicated significant TCRβ repertoire similarity between tumor and blood in distant-metastatic patients (comparison with nonmetastasis, P < .05). According to the discrepancy of the CDR3 among patients with different clinicopathological status, the classifier was constructed to discriminate distant-metastatic individuals. A promising area under the curve value of 83.8% was obtained with the number of overlapping CDR3 clonotypes., Conclusion: The availability and reliability of TCR-seq render it prospective to translate these intrinsic attributes into clinical practice for monitoring distant metastasis in PTC patients., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland, with a relatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, it significantly decreases the survival of PTC patients. The molecular mechanisms of DM in PTC have not been systematically studied. We performed whole exome sequencing and GeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched white blood cell samples from 20 PTC with DM and 46 PTC without DM. We identified somatic mutations, gene fusions and copy number alterations and analyzed their relationships with DM of PTC. BRAF-V600E was identified in 73% of PTC, followed by RET fusions (14%) in a mutually exclusive manner (P < 0.0001). We found that gene fusions (RET, ALK or NTRK1) (P < 0.01) and chromosome 22q loss (P < 0.01) were independently associated with DM in both univariate and multivariate analyses. A nomogram model consisting of chromosome 22q loss, gene fusions and three clinical variables was built for predicting DM in PTC (C-index = 0.89). The plasma circulating tumor DNA (ctDNA) detection rate in PTC was only 38.9%; however, it was significantly associated with the metastatic status (P = 0.04), tumor size (P = 0.001) and invasiveness (P = 0.01). In conclusion, gene fusions and chromosome 22q loss were independently associated with DM in PTC and could serve as molecular biomarkers for predicting DM. The ctDNA detection rate was low in non-DM PTC but significantly higher in PTC with DM., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Circular RNA (circRNA) is a new type of noncoding RNA that can serve as ideal biomarkers. Evidence has showed that circRNAs play an important role in carcinogenesis and cancer development. However, little is known about the diagnostic value of circRNAs in papillary thyroid carcinoma (PTC) as well as their associations with clinicopathologic characteristics of patients with PTC., Methods: The expression levels of hsa&#95;circ&#95;0137287 were detected in 120 PTC and 60 adjacent noncancerous thyroid tissues by quantitative real-time polymerase chain reaction. The relationships between the expression of hsa&#95;circ&#95;0137287 in PTC and the clinicopathologic factors were analyzed. Finally, receiver operating characteristic (ROC) curves were generated to assess the diagnostic value of hsa&#95;circ&#95;0137287 as a biomarker for PTC., Results: The expression of hsa&#95;circ&#95;0137287 was significantly downregulated in PTC tissues compared with adjacent noncancerous tissues (P < .0001). Downregulation of hsa&#95;circ&#95;0137287 correlated with aggressive clinicopathologic characteristics of PTC such as extrathyroidal extension (P < .001), lymph node metastasis (P = .022), advanced T stage (P < .001) and larger tumor size (P < .001). The ROC curves revealed that hsa&#95;circ&#95;0137287 had a potential diagnostic value in predicting malignancy, extrathyroidal extension and lymph node metastasis. The area under curves were 0.8973 (95% CI = 0.8452-0.9494, P < .0001), 0.6885 (95%CI = 0.5908-0.7862, P = .0009), and 0.6691(95%CI = 0.5641-0.7742, P = .0034), respectively., Conclusions: Our findings suggest that hsa&#95;circ&#95;0137287 may serve as a novel biomarker for PTC., (© 2018 Wiley Periodicals, Inc.)

Background/aims: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, the molecular mechanisms responsible for its tumorigenesis and progression remain largely unknown. Circular RNA (circRNA) is a novel type of noncoding RNA that can serve as an ideal biomarker due to its stability. Recent evidence suggests that circRNAs play important roles in tumorigenesis. This study aims to investigate circRNA expression profiles and their potential biological functions in PTC., Methods: High-throughput RNA sequencing was used to assess circRNA expression profiles in PTC, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate dysregulated circRNAs. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of circRNAs for PTC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed circRNAs. Bioinformatic analyses were applied to predict interactions between circRNAs and microRNAs (miRNAs), and a circRNA-miRNA-mRNA network was constructed using Cytoscape software., Results: We identified a number of differentially expressed circRNAs in PTC tissues compared with paired normal thyroid tissues, with chr5: 160757890-160763776-, chr12: 40696591-40697936+, chr7: 22330794-22357656-, and chr21: 16386665-16415895- being upregulated, and chr7: 91924203-91957214+, chr2: 179514891-179516047-, chr9: 16435553-16437522-, and chr22: 36006931-36007153- being downregulated. These findings were confirmed by qRT-PCR, and ROC curves indicated that they can serve as potential biomarkers for PTC. GO and KEGG pathway analyses showed that some of these circRNAs are related to cancers. Additionally, bioinformatic analyses revealed a potential competing-endogenous-RNA-regulating network among circRNAs, miRNAs, and mRNAs., Conclusions: Our study results depict the landscape of circRNA expression profiles in PTC and also provide potential biomarkers for PTC. Further functional and mechanistic studies of these circRNAs may improve our understanding of PTC tumorigenesis., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background: H2AX, one of the variants of histone H2A with conserved sequence, plays a vital role in maintaining genomic stability. DNA double-strand break (DSB) induces H2AX phosphorylation (γH2AX). Growing evidence indicated γH2AX was linked to thyroid disease. However, the precise expression of γH2AX in papillary thyroid carcinoma (PTC) and nodular goiter was unknown. In this study, the yH2AX expression in PTC and nodular goiter and the significance of the aberrant expression were investigated., Methods: The γH2AX expression level was evaluated by immunohistochemistry staining in 140 specimens with thyroid diseases (30 cases of nodular goiter, 30 cases of PTC, and 80 cases of PTC coexisting with nodular goiter). The possible relationships between γH2AX expression and patients' clinicopathological characteristics were analyzed., Results: In the set of nodular goiter, 20.0% (6/30) of nodular goiter component and 10.0% (3/30) of normal adjacent tissues exhibited high expression of γH2AX (p > 0.05). In the set of PTC, 70.0% (21/30) of PTC component and 0.0% (0/30) of normal adjacent tissues showed high expression of γH2AX (p < 0.05). In the set of PTC coexisting with nodular goiter, 95.0% (76/80) of PTC component, 12.5% (10/80) of nodular goiter component, and 8.8% (7/80) of normal adjacent specimens showed high expression of γH2AX (p < 0.05). 85.5% (65/76) of PTC patients with lymph node metastasis were found to have a high expression level of γH2AX, and the proportion was lower than that in patients without lymph node metastasis (34/34, 100.0%) (p = 0.003). High γH2AX expression was also found in 76.2% (16/21) of stage IV patients and the proportion was lower than that in stage I - III patients (83/89, 93.3%) (p = 0.034). No statistically significant correlation was found between yH2AX expression level and other clinicopathological features, including age, gender, capsular invasion, tumor size, tumor focus number, distant metastasis, and T status., Conclusions: γH2AX expression was increased in PTC patients, while nodular goiter and normal adjacent tissues exhibited no statistically significant difference in γH2AX expression. yH2AX expression had a negative correlation with TNM stage and lymph node metastasis. γH2AX seems to play a more critical role in early-stage PTC rather than late-stage PTC and might inhibit lymph node metastasis.