Papillary Thyroid Carcinoma: Correlation Between Molecular and Clinical Features.

BACKGROUND: Thyroid cancer is prevalent worldwide, including in China, where its incidence is on the rise. Papillary thyroid carcinoma (PTC) is the predominant subtype. Investigating the relationship between clinical data associated with PTC and gene mutations is crucial for improving detection and treatment. PATIENTS AND METHODS: We collected samples and associated clinical data from 700 PTC patients at Shanxi Provincial People's Hospital. Using a panel of 57 genes linked to thyroid cancer, we sequenced the samples to determine the mutation frequency of thyroid cancer-associated genes in PTC. We further analyzed the correlation between gene variants and clinical information. RESULTS: The mean age of patients in this study was 42.5 years. Females predominated, comprising 507 of the total patient population, resulting in a female-to-male ratio of 2.63 (507:193). Tumor distribution revealed 198, 257, and 142 cases on the left, right, and both sides, respectively. Among the 57 thyroid cancer-related genes analyzed, we identified at least one driver gene in 83.6% of patients. Notably, 76.4% had BRAF mutations, mainly BRAFV600E, which constituted 90.9% of all BRAF mutations, with 535 cases exhibiting these mutations. Other significant driver genes included CHEK2 (n = 84), RET (n = 42), PIK3CA (n = 7), and EGFR (n = 7). RET fusions (n = 28) were also identified. Notably, patients under 55 years old exhibit a higher tendency towards advanced N staging, suggesting that younger individuals may be more prone to lymph node metastasis. Additionally, male patients were more likely to have advanced N stages. Importantly, a positive correlation was observed between higher BRAF allele frequencies and more advanced T and N stages. Similarly, correlation analysis revealed that a greater frequency of RET fusions correlated with later T and N stages. CONCLUSION: This study uncovered several significant insights. Younger PTC patients exhibited a higher propensity for lymph node metastasis. An elevated mutation frequency of BRAF was correlated with a higher occurrence of RET fusions, predisposing individuals to lymph node metastasis and potentially indicating a poorer prognosis.

Effect of disulfidptosis-related genes SLC3A2, SLC7A11 and FLNB polymorphisms on risk of autoimmune thyroiditis in a Chinese population.

PURPOSE: This study aimed to evaluate the associations between disulfidptosis related genes-SLC3A2, SLC7A11 and FLNB polymorphisms and risk of autoimmune thyroiditis (AIT). METHODS: Six SNPs in the SLC3A2, SLC7A11 and FLNB were genotyped in 650 AIT cases and 650 controls using a MassARRAY platform. RESULTS: Minor alleles of SLC3A2-rs12794763, rs1059292 and FLNB-rs839240 might lead to a higher risk of AIT (p < 0.001), while SLC7A11-rs969319-C allele tends to decrease the risk of the disease (p = 0.006). Genetic model analysis showed that SLC3A2-rs12794763, SLC3A2-rs1059292 and FLNB-rs839240 polymorphisms were risk factors for AIT (p < 0.001); while SLC7A11-rs969319 showed a protective role for the disease in all genetic models (p < 0.005). Stratification analysis showed that SLC3A2-rs1059292 and rs12794763 were correlated with higher risk of AIT regardless of sex (p < 0.05). Moreover, FLNB-rs839240 exhibited higher risk of disease only in females (p < 0.05). By contrast, SLC7A11-rs969319 showed a protective role only in females (p < 0.05). CONCLUSION: Our results shed new light on the association between disulfidptosis-related genes and AIT risk.

CircSND1/miR-182-5p Axis Promotes Proliferative and Invasive Abilities of Thyroid Cancer via Binding Targeting MET.

Objective: To monitor the impacts of circSND1 upon thyroid cancer (TC) tissues and cells and its mechanisms. Methods: Thiazole blue (MTT) was adopted to monitor the impacts of circSND1 upon the proliferative abilities of TPC-1 and SW1736 cells. 5-Bromodeoxyuridine (BrdU) combined with flow cytometry was adopted to monitor the impacts of circSND1 upon the DNA synthesis of TPC-1 and SW1736 cells. We adopted transwell experiment to examine the impacts of circSND1 on cell invasive abilities of TPC-1 and SW1736 cells. The mRNA quantitative levels of circSND1, miR-182-5p, and mesenchymal epidermal transformation factor (MET) in TC tissues were detected by qRT-PCR experiment. We also adopted luciferase assay to verify the targeting interaction between miR-182-5p and MET or miR-182-5p and circSND1. Results: CircSND1 mRNA and MET mRNA were upregulated in thyroid cancer tissues. MiR-182-5p quantification was attenuated in thyroid cancer tissues. Downregulation of circSND1 suppressed TC progression in vivo and in vitro. Furthermore, luciferase report assay uncovered that miR-182-5p was a direct binding target of circSND1 and MET was a direct binding target of miR-182-5p. Besides, circSND1 regulated MET expression and thyroid cancer cell function via binding miR-182-5p. Conclusion: Overexpression of circSND1 in TC tissues and cells facilitates TC tumorigenesis and metastasis via suppressing the quantitative level of miR-182-5p and inducing the upregulation of MET mRNA and protein expression, which expected to offer fresh clues for the administration of TC.

Ferroptosis-Related APOE, BCL3 and ALOX5AP Gene Polymorphisms are Associated with the Risk of Thyroid Cancer.

PURPOSE: This study aimed to evaluate the association between polymorphisms in the ferroptosis-related genes apolipoprotein E (APOE), BCL3 transcription coactivator (BCL3) and arachidonate 5-lipoxygenase activating protein (ALOX5AP) and the risk of thyroid cancer. METHODS: Six single nucleotide polymorphisms (SNPs) of APOE (rs429358 and rs7412), BCL3 (rs34698726 and rs8100239) and ALOX5AP (rs4076128 and rs4073259) were genotyped in 520 papillary thyroid carcinoma cases and 520 healthy controls using the MassARRAY platform. RESULTS: The rs429358-TC, rs34698726-TA/TT, and rs8100239-AT/AA genotypes exhibited an elevated risk of thyroid cancer (p rs429358 = 0.002, p rs34698726 = 0.007, p rs8100239 = 0.002), while rs7412-CT/TT and rs4076128-GA/GG were found to be protective genotypes against the risk of disease (p rs7412 = 0.0003, p rs4076128 = 0.0001). Genetic model analysis showed that APOE-rs429358 was correlated with an increased risk of disease under dominant and log-additive models (p dominant = 0.0004, p log-additive = 0.0006). BCL3-s34698726 and rs8100239 were associated with an elevated risk of disease under all three genetic models (p < 0.05). In contrast, APOE-rs7412 was related to a decreased risk of thyroid cancer under dominant and log-additive models (p dominant = 0.0001, p log-additive = 0.0001). Moreover, ALOX5AP-rs4076128 was also correlated with a reduced risk of disease under all three genetic models (p < 0.05). CONCLUSION: The results help us better understand how genetic polymorphisms in ferroptosis-related genes are relevant to thyroid cancer susceptibility.

Oncolytic Vaccinia Virus-Mediated Antitumor Effect and Cell Proliferation Were Promoted in PTC by Regulating circRNA_103598/miR-23a-3p/IL-6 Axis.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy, and cases have been rising steadily worldwide in the past few decades. Despite great progress having been made in surgery and chemotherapy for PTC, the survival rate of PTC patients has not increased significantly. Therefore, there is an urgent need to explore novel treatment strategies. MATERIALS AND METHODS: The levels of circRNA_103598, miR-23a-3p and IL-6 mRNA in PTC tissues and cells were examined by qRT-PCR assay. Cell proliferation and IC50 values of oncolytic vaccinia virus (OVV) were detected by CCK-8 assay. A dual-luciferase reporter assay was performed to detect the relationships among circRNA_103598, miR-23a-3p and IL-6. ELISA was carried out to detect the expression of IL-6. RESULTS: We found that circRNA_103598 was increased in PTC tissues and cell lines and acted as a sponge for miR-23a-3p. Moreover, knockdown of miR-23a-3p suppressed the OVV-mediated antitumor effect and cell proliferation in PTC. In addition, we revealed that circRNA_103598 bound to miR-23a-3p as a sponge to promote IL-6 expression. CONCLUSION: Our study first revealed the high expression and oncogenic function of circRNA_103598 in PTC cells. Then, circRNA_103598 sponged miR-23a-3p to upregulate IL-6 expression, with the resulted that cell proliferation was promoted and the OVV-mediated antitumor effect was enhanced by strengthening the viral replication, providing new insights into future therapy for PTC.

Revealing gene clusters associated with the development of cholangiocarcinoma, based on a time series analysis.

Cholangiocarcinoma (CC) is a rapidly lethal malignancy and currently is considered to be incurable. Biomarkers related to the development of CC remain unclear. The present study aimed to identify differentially expressed genes (DEGs) between normal tissue and intrahepatic CC, as well as specific gene expression patterns that changed together with the development of CC. By using a two­way analysis of variance test, the biomarkers that could distinguish between normal tissue and intrahepatic CC dissected from different days were identified. A k­means cluster method was used to identify gene clusters associated with the development of CC according to their changing expression pattern. Functional enrichment analysis was used to infer the function of each of the gene sets. A time series analysis was constructed to reveal gene signatures that were associated with the development of CC based on gene expression profile changes. Genes related to CC were shown to be involved in 'mitochondrion' and 'focal adhesion'. Three interesting gene groups were identified by the k­means cluster method. Gene clusters with a unique expression pattern are related with the development of CC. The data of this study will facilitate novel discoveries regarding the genetic study of CC by further work.