Papillary Thyroid Carcinoma Invasion Research Articles

Characterization of microRNA-223-3p as a novel promoter of cell proliferation and invasion in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC), the most common thyroid cancer, has been linked to various molecular alterations. This study focuses on microRNA-223-3p, whose upregulated expression in PTC tissues appears to enhance tumor growth and cellular dysfunctions. Our findings demonstrate that microRNA-223-3p significantly promotes cell proliferation, invasion, and migration and induces epithelial-mesenchymal transition (EMT). Additionally, neurofibromatosis type 2 (NF2) is identified as a direct target, suggesting that microRNA-223-3p could be crucial in PTC pathogenesis and may offer a target for therapeutic intervention.

Estrogen enhances the proliferation, migration, and invasion of papillary thyroid carcinoma via the ERα/KRT19 signaling axis.

Estrogen is thought to be the reason for the higher prevalence of papillary thyroid carcinoma (PTC) in fertile women; however, more study is required to completely comprehend how estrogen affects PTC development at the cellular level. Therefore, we combined Oxford Nanopore Technologies (ONT) sequencing to explore molecular markers of PTC and to investigate the molecular mechanisms by which estrogen promotes PTC development. The expression levels of ESR1 (ERα) and KRT19 in normal thyroid tissues and cancer tissues as well as in different cancer stages, races, genders, age groups, histological subtypes and nodular metastasis status of the TCGA database were analyzed online by Ualcan; the relationship between ESR1, KRT19 and the survival of THCA patients was analyzed. A PTC xenograft tumor model was established. An ERα specific inhibitor (MPP) was administered and an EDU cell proliferation assay was used to verify the effect of estrogen on PTC proliferation. KRT19 was knocked down in KTC-1 cells, and the proliferation, migration, and invasion abilities of PTC cells were determined using CCK-8, immunofluorescence labeling, Western blot for EMT-related proteins, scratch assay, and Transwell assay. The role of ERα in relation to KRT19 was investigated by Western blot and immunofluorescence. The effects of ERα/KRT19 signaling axis on the proliferation, migration and invasion ability of PTC cells were evaluated using EDU cell proliferation assay and Transwell. Using ONT sequencing, 15 pairs of PTC tissue and paracancer tissue samples were collected. A PPI network was constructed to validate the differential expression of KRT19 in combination with biosignature analysis, and the protein interaction between KRT19 and ESR1 was verified using STRING. Ualcan showed that the expression of ESR1 and KRT19 was higher in THCA tissues than in normal thyroid tissues. E2 activation of ERα promoted the growth of PTC cells and tissues. si-KRT19 inhibited the proliferation, migration and invasion of PTC cells. KRT19 together with ERα formed the ERα/KRT19 signaling axis. E2 activation of the ERα/KRT19 signaling axis promoted the proliferation, migration, and invasion of PTC cells. ONT sequencing and STRING website verified that KRT19 is significantly differentially expressed in PTC and that ESR1 and KRT19 have protein interactions and are related to the estrogen signaling pathway. Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion.

HNRNPC modulates PKM alternative splicing via m6A methylation, upregulating PKM2 expression to promote aerobic glycolysis in papillary thyroid carcinoma and drive malignant progression.

The heterogeneous nuclear ribonucleoprotein C (HNRNPC) plays a crucial role in tumorigenesis, yet its role in papillary thyroid carcinoma (PTC) remains elusive. Herein, we elucidated the function and molecular mechanism of HNRNPC in PTC tumorigenesis and progression. Our study unveiled a significant upregulation of HNRNPC in PTC, and knockdown of HNRNPC markedly inhibited the proliferation, invasion, and metastasis of BCPAP cells. Furthermore, HNRNPC modulated PKM alternative splicing in BCPAP cells primarily through m6A modification. Additionally, by upregulating PKM2 expression, HNRNPC promoted aerobic glycolysis in BCPAP cells, thereby facilitating malignant progression in PTC. In summary, our findings demonstrate that HNRNPC regulates PKM alternative splicing through m6A methylation modification and promotes the proliferation, invasion and metastasis of PTC through glucose metabolism pathways mediated by PKM2. These discoveries provide new biomarkers for screening and diagnosing PTC patients and offer novel therapeutic targets for personalized treatment strategies.

Decreased sirtuin 4 levels promote cellular proliferation and invasion in papillary thyroid carcinoma.

This study examined the effect of sirtuin 4 (SIRT4), a NAD+-dependent deacetylase, on the proliferation and progression of papillary thyroid carcinoma (PTC). Data from The Cancer Genome Atlas (TCGA) were analyzed to identify SIRT4 expression in thyroid cancer. Subsequently, the correlation between SIRT4 expression and clinical characteristics was examined in 205 PTC tissue samples. In vitro assays using three human thyroid cancer cell lines (B-CPAP, TPC-1, and SNU-790) were conducted to assess the effects of regulated SIRT4 expression on cell growth, apoptosis, invasion, and migration. Furthermore, in vivo experiments were performed in a xenograft mouse model. Gene Expression Omnibus (GEO) and TCGA data indicated that SIRT4 expression is lower in thyroid cancer and SIRT4 downregulation is associated with poor overall survival. In PTC tissues, positive SIRT4 expression was associated with decreased extracapsular extension. In in vitro experiments using three human thyroid cancer cell lines, overexpression of SIRT4 decreased cell survival, clonogenic potential, and invasion and migratory capabilities, as well as inducing apoptosis and increasing reactive oxygen species levels. SIRT4 overexpression upregulated E-cadherin and downregulated N-cadherin, suggesting its potential involvement in the regulation of epithelial-mesenchymal transition. These findings were confirmed in vivo using a xenograft mouse model. This study provides novel insight into the potential contribution of SIRT4 to the regulation of the pathological progression of PTC. The data suggest that SIRT4 plays a tumor-suppressive role in PTC by inhibiting growth, survival, and invasive potential. Future research should investigate the molecular mechanisms underlying these effects of SIRT4.

Defining angioinvasion and lymphatic invasion in papillary thyroid carcinoma: morphological criteria, utility of D2-40/CD31/ERG immunohistochemistry and correlation with clinicopathological characteristics.

While CAP and ICCR protocols mandate the separation of angioinvasion (AI) and lymphatic invasion (LI) in thyroid carcinoma, distinction between them can be difficult. Because the presence of AI is used to stratify patients with papillary thyroid carcinoma (PTC), there is a need to accurately diagnose AI and LI. AI and LI were evaluated in 162 cases of PTC (n = 155) and high-grade differentiated thyroid carcinoma, papillary phenotype (HGDTCp, n = seven) using haematoxylin and eosin (H&E), D2-40 and CD31/ERG. In encapsulated carcinomas, vascular invasion (VI) was only of AI nature. Infiltrative carcinomas showed LI (46 of 131, 35%) and AI (19 of 131, 16%). The frequency of nodal metastasis (NM) and large volume of NM was 93 and 85%, respectively, in tumours with LI, and 39 and 26%, respectively, in those without LI. Luminal red blood cells and smooth muscle in the wall of large-calibre vessels were not reliable criteria to exclude LI and were seen in 23 and 6% of LI, respectively. LI was an independent predictor for NM, whereas AI is an independent predictor for distant metastasis at presentation in PTC/HGDTCp. VI in encapsulated carcinomas, including follicular variant PTC, is only of AI nature, confirming the position of this variant as a close entity to follicular carcinoma rather than classic PTC, whereas infiltrative PTC/HGDTCp may have LI or, less frequently, AI. As no morphological features reliably distinguish LI from AI, D2-40 and CD31/ERG immunostains should be considered for separating AI from LI when dealing with vascular invasion in an infiltrative PTC.

CircPHGDH downregulation decreases papillary thyroid cancer progression through miR-122-5p/PKM2 axis

BackgroundAlthough papillary thyroid carcinoma (PTC) has a favorable prognosis, it could affect patient life quality and become a serious threat because of invasion and metastasis. Many investigations have suggested that circular RNAs (circRNAs) are involved in different cancer regulations. Nevertheless, circRNAs role in invasive PTC remains unclear.MethodsIn the present investigation, next-generation sequencing was applied to explore abnormal circRNA expression. The expression of circRNA phosphoglycerate dehydrogenase (circPHGDH) in PTC cell lines and tissues were examined. Then, we investigated regulatory mechanism and circPHGDH downstream targets using bioinformatics analysis and luciferase reporting analysis. Then transwell migration, Cell Counting Kit-8 (CCK8) and 5-ethynyl-2’-deoxyuridine (EdU) assays were used for cells migration and proliferation analysis. In vivo metastasis and tumorigenesis assays were also employed to evaluate the circPHGDH role in PTC.ResultsThe data showcased that circPHGDH expression increased in both PTC cell lines and tissues, which suggested that circPHGDH functions in PTC progression. circPHGDH downregulation suppressed PTC invasion and proliferation in both in vivo and in vitro experiments. Bioinformatics and luciferase reporter results confirmed that both microRNA (miR)-122-5p and pyruvate kinase M2 subtype (PKM2) were downstream targets of circPHGDH. PKM2 overexpression or miR-122-5p suppression reversed PTC cell invasion and proliferation post silencing circPHGDH by restoring aerobic glycolysis.ConclusionTaken together, our research found that circPHGDH downregulation reduced PTC progression via miR-122-5p/PKM2 axis regulation mediated by aerobic glycolysis.

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

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

Circ-LDLRAD3/miR-655-3p/MAPK1 axis enhances cell migration and invasion in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a prevalent histological subtype of thyroid cancer, whose occurrence and development may be related to circRNA dysregulation. This research proposed to unravel circ-LDLRAD3-related mechanisms in PTC. First, circ-LDLRAD3, miR-655-3p .and MAPK1 levels in PTC were quantitatively measured. Then, plasmid vectors or oligonucleotides that interfere with circ-LDLRAD3, miR-655-3p, or MAPK1 were transfected into PTC cells, followed by the analysis of proliferation, apoptosis, migration, and invasion. Finally, the targeted binding sites between miR-655-3p and circ-LDLRAD3 or MAPK1 were predicted by starBase and experimentally verified. Statistically, PTC samples expressed high circ-LDLRAD3 and MAPK1 and low miR-655-3p. Knocking down circ-LDLRAD3 or enhancing miR-655-3p hindered PTC cell proliferation, migration, and invasion, and forced apoptosis. circ-LDLRAD3 bound to miR-655-3p to affect MAPK1 expression. Elevating MAPK1 rescued circ-LDLRAD3 knockdown-allowed obstruction of PTC cell growth. In conclusion, circ-LDLRAD3 stimulates PTC development by releasing miR-655-3p-targeted MAPK1.

The association between integrin β4 overexpression and lymphovascular invasion in papillary thyroid cancer.

Lymphovascular invasion is an independent prognostic marker in papillary thyroid carcinomas. In addition, integrin β4 is associated with advanced progression and metastasis in many malignancies. We aimed to investigate the relationship between integrin β4 and lymphovascular invasion in papillary thyroid carcinoma. 73 patients with papillary thyroid cancer (48 patients with lymphovascular invasion and 25 patients without) were included in our study. The immunohistochemical staining score for integrin b4 was evaluated according to the percentage and intensity of staining. The staining intensity was scored as 0 (no staining), 1 (weak staining - light yellow), 2 (medium staining - yellow-brown), and 3 (strong staining - brown). The staining was scored by multiplying the percentage and intensity of staining. The mean percentage of integrin b4 staining was 63.54 ± 22.26% in the group with lymphovascular invasion and 10.2 ± 22.48% in the group without lymphovascular invasion (p < 0.001). When evaluated in terms of staining score, it was found to be 107.08 ± 45.29 in the group with lymphovascular invasion and 16.2 ± 40.03 in the group without lymphovascular invasion (p < 0.001). There was a linear relationship between the percentage of integrin β4 and the staining scores (r² = 0.881; p < 0.001). In the by receiver-operating characteristic (ROC) curve analysis for the cut-off value of the percentage of integrin b4 staining, the area under the curve was found to be 0.916. The cut-off value for the percentage of integrin b4 was found to be 35 (sensitivity 91.7% and specificity 88%) (odds 80.66%). A significant relationship was found between integrin b4 expression and lymphovascular invasion in papillary thyroid carcinomas. Integrin b4 expression level can be used as a marker to predict the presence of lymphovascular invasion in papillary thyroid carcinomas, especially in large tumours where it may not be possible to sample the entire tumour.

MicroRNA-3653-3p inhibited papillary thyroid carcinoma progression by regulating CRIPTO-1.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignant tumor and the metastasis of PTC often leads to unfavorable prognosis. Thus, the purpose of the current research was to mainly explore the role of miR-3653-3p in PTC progression. The expression level of miR-3653-3p in PTC was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and Cell Counting Kit-8 (CCK-8) assay and colony formation assay were recruited to assess the ability of miR-3653-3p on cell proliferation. Next, transwell assay and Matrigel assay were involved to examine the ability of miR-3653-3p on cell migration and invasion. At last, Dual-Luciferase reporter assay and Western blotting were recruited to validate the down-stream target of miR-3653-3p. Results showed that miR-3653-3p was down-expressed in PTC, and upregulated miR-3653-3p inhibited cell proliferation, cell migration, and cell invasion in vitro. In addition, CRIPTO-1 was a downstream target of miR-3653-3p, and miR-3653-3p inhibited PTC progression via regulating CRIPTO-1. In sum, this research verifies that miR-3653-3p suppresses cell proliferation, migration, and invasion in PTC via regulating CRIPTO-1. These findings provide new insight into the underlying mechanism of PTC progression and may be useful in finding biomarkers and therapeutic targets of PTC.

The relationship between subclinical hypothyroidism and invasive papillary thyroid cancer.

Subclinical hypothyroidism is the most common thyroid dysfunction. Approximately 10% of patients with thyroid cancer have subclinical hypothyroidism. There is a paucity of real-world studies examining the relationship between subclinical hypothyroidism and known correlates of invasiveness of papillary thyroid carcinoma (PTC). A retrospective cohort study of 13,717 patients with PTC was conducted. Odds ratios were calculated to assess the relationship between subclinical hypothyroidism and extrathyroidal extension (ETE) after adjusting for BMI and genders. The Cancer Genome Atlas (TCGA) data were utilized for the analysis of TSHR-associated pathways, while qRT-PCR was employed to validate the expression levels of pivotal genes in the relevant signaling pathways. In total, 13,717 PTC patients (10,769 women and 2,948 men; mean [SD] age, 42.90 [9.43] years) were included in the retrospective study. Subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.168 [95% CI, 1.028-1.327]; P=0.017). In normal-weight patients, subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.287 [95% CI, 1.089-1.520]; P=0.003). However, this risk was not observed in under-weight, overweight, and obese patients. Compared to females, subclinical hypothyroidism was a higher risk factor for ETE in male patients with normal body weight (OR male=2.363 vs. OR female=1.228). Subclinical hypothyroidism was found to be a significant risk factor for ETE in the subgroup of patients younger than 38 years old (OR1 adjusted, 1.382 [95% CI, 1.032-1.852], P=0.030). The findings from Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the involvement of the autophagy signaling pathway in TSHR/ETE/EMT regulation. Moreover, the gene expression levels demonstrated a concentration-dependent relationship between TSH intervention levels and the expression of key genes in the autophagy pathway of thyroid cancer cells. Subclinical hypothyroidism was an independent risk factor for ETE in patients with PTC. This association was particularly significant in normal-weight and younger patients. The risk of ETE associated with subclinical hypothyroidism was higher in males compared to females. Our study indicates a potential involvement of the autophagy pathway in regulating the ETE phenotype in thyroid cancer, specifically in the context of subclinical hypothyroidism.

TRPC5 expression promotes the proliferation and invasion of papillary thyroid carcinoma through the HIF-1α/Twist pathway

ObjectiveThis study aimed to investigate the effect of TRPC5 on PTC (papillary thyroid carcinoma) proliferation and invasion. MethodsImmunofluorescence and western blot were used to evaluate the expression of TRPC5 in paraffin sections and clinical tissues. Overexpression and silencing of TRPC5 to generate the cells for in vitro experiments. Wound-healing assay, transwell invasion assay, MTT assay, and in vivo tumorigenicity assay were used to determine cell proliferation and cell migration in vitro and in vivo. Real-time PCR was used to test the expression of TRPC5. Western blot was used to test the expression of downstream factors: E-cadherin, Vimentin, MMP-9, MMP-2, TRPC5, ZEB, Snail, and Twist. ResultsThe level of TRPC5 protein expression was higher in PTC than in adjacent normal thyroid tissue. TPC-1 cells overexpressing TRPC5 were more proliferative, had longer migration distances, and increased the number of invading cells. TPC-1 cells silenced with TRPC5 had a weaker proliferation capacity, shorter migration distances, and a reduced number of invading cells. Overexpression and silencing of TRPC5 modulated E-cadherin, Vimentin, MMP-9, MMP-2, TRPC5, and Twist, but did not affect ZEB and Snail. The results of tumor formation experiments in nude mice showed that inhibition of TRPC5 expression suppressed the volume and weight of transplanted tumors. ConclusionTRPC5 induced papillary thyroid cancer metastasis and progression via up-regulated HIF-1α signaling in vivo and in vitro. High TRPC5 expression is a biomarker for lymph node metastasis at its early stages.

Shaving Papillary Thyroid Carcinoma Involving Functioning Recurrent Laryngeal Nerve: Safety of Incomplete Tumor Resection and Nerve Sparing.

Whether to sacrifice or spare the recurrent laryngeal nerve (RLN) when papillary thyroid carcinoma (PTC) involves a functioning RLN remains controversial. Oncological outcomes after shaving PTC with gross remnant on the RLN have been rarely reported. The objective of this study was to evaluate the oncological outcomes of patients who underwent shaving of a PTC from the RLN, leaving a gross residual tumor with the intent of vocal function preservation. A retrospective, cohort study was conducted in 47 patients who were determined to have PTC invasion of the RLN via intraoperative inspection and underwent tumor shaving with macroscopic remnant (R2 resection) less than 1 cm in length and 4 mm in thickness. Median follow-up period was 93 (range, 60-215) months. The primary endpoint was the recurrence-free survival and the progression-free survival. Secondary endpoints were biochemical outcomes (serum thyroglobulin) and vocal cord function. Of the 47 patients, five (10.6%) patients showed recurrence (central neck, 3; lateral neck, 2) without death or distant metastasis. The RLN was resected along with the tumor in one (2.1%) patient who presented with progression of the residual tumor. Postoperative temporary vocal cord paralysis occurred in six (12.8%) patients without permanent cases. The final nonstimulated serum thyroglobulin was 0.7 ± 1.8 ng/ml. Shaving a tumor from a RLN with gross residual disease may be considered an alternative strategy to preserve vocal function when complete tumor resection with nerve preservation is impossible in patients with PTC invading a functioning RLN.

The diagnostic potential of two exosome-derived circRNAs for papillary thyroid cancer.

As a critical component of exosomes, circular RNAs (circRNAs) have shown great value in cancer diagnosis. This study aimed to identify circRNAs in exosomes for the diagnosis of PTC (papillary thyroid carcinoma). We selected hsa_circ_0082002 and hsa_circ_0003863 based on circRNA microarray. The levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 in the sera of healthy control (n = 68), benign thyroid tumors (n = 60), and PTC without and with Hashimoto's thyroiditis (n = 164) were quantified by qPCR (quantitative polymerase chain reaction). Receiver operating characteristic analyses were conducted to evaluate the diagnostic sensitivity and specificity. Bioinformatics databases were used to predict the microRNAs and proteins binding with hsa_circ_0082002 and hsa_circ_0003863. The levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 were positively associated and statistically increased in PTC compared to healthy and benign thyroid tumors. Intriguingly, higher levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 were positively correlated with lymph node metastasis and vascular invasion in PTC. Further stability tests show that exosomal hsa_circ_0082002 and hsa_circ_0003863 could exist stably in sera treated by several freeze-thaw cycles at -20°C and with a storage time shorter than 24h at 4°C. Furthermore, hsa_circ_0082002 and hsa_circ_0003863 were predicted to interact with microRNAs and proteins, suggesting that hsa_circ_0082002 and hsa_circ_0003863 might contribute to the occurrence and progression of PTC through interacting with microRNAs and RNA binding proteins. Collectively, we identified two PTC-related circRNAs incorporated in exosomes and uncovered their potential as tumor markers to diagnose PTC, in particular, more aggressive PTC.

Circ_LDLR promotes the progression of papillary thyroid carcinoma by regulating miR-1294/HMGB3 axis.

Circular RNAs (circRNAs) have been found to be associated with the development and progression of cancers including papillary thyroid carcinoma (PTC). Circ_LDLR has been reported to be highly expressed in PTC, but its underlying mechanism of action has not been fully elucidated. This study aimed to investigate the role of circ_LDLR in PTC. The expression of circ_LDLR, miR-1294 and high mobility group box (HMGB) 3 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). CCK-8 assay and transwell assays were employed to value cell viability, invasion and migration abilities. Western blot assay was to detect HMGB3 protein expression. Luciferase reporter gene and pull down assay were used to validate the interaction between miR-1294 and HMGB3 or circ_LDLR. Circ_LDLR showed high expression levels in PTC tissues and cells and knockdown of it inhibited the growth, invasion, and migration of PTC cells. In addition, miR-1294 was considered as a downstream target of circ_LDLR, and inhibition of miR-1294 partially reversed the inhibitory effects of circ_LDLR knockdown on PTC cells growth, invasion, and migration. More importantly, HMGB3 was identified as a downstream target of miR-1294. Our findings suggest circ_LDLR may plays a promoting role in PTC by downregulating miR-1294 and upregulating HMGB3 expression. Therefore, circ_LDLR may serve as a valuable prognostic biomarker and therapeutic target for PTC.

Profile of BRAFV600E, BRAFK601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital.

BRAFV600E and RAS mutations are the most common gene mutations in papillary thyroid carcinoma (PTC) that may be correlated with its biological behavior. There are still limited data about BRAFV600E and RAS mutations in Indonesia. This study aims to determine the prevalence of BRAFV600E and RAS mutations, and their association with clinicopathologic characteristics. Patients who had total thyroidectomy from 2019 to 2021 and those who met our study criteria underwent PCR and DNA sequencing analysis for BRAFV600E, BRAFK601E, exon 2 and 3 of NRAS, HRAS, and KRAS. Analyses were performed to determine the associations of BRAFV600E and RAS mutations with clinicopathologic characteristics. Of 172 PTC patients, BRAFV600E mutation was observed in 37.8% of the patients and RAS mutations were found in 21.5%. One patient harbored BRAFK601E mutation. There was a significant association of BRAFV600E with a high-stage (p = 0.033, OR: 3.279; 95% CI: 1.048-10.259), tall-cell variants (p ≤0.001, OR: 41.143; 95% CI: 11.979-141.308), non-encapsulated (p = 0.001, OR: 4.176; 95% CI: 2.008-8.685), lymphovascular invasion (p = 0.043, OR: 1.912; 95% CI: 1.018-3.592), extrathyroidal extension (p = <0.001, OR: 3.983; 95% CI: 1.970-8.054), and lymph node metastasis (p = 0.009, OR: 2.301; 95% CI: 1.224-4.326). Follicular variant (p = 0.001, OR: 7.011; 95% CI: 2.690-18.268), encapsulated (p = 0.017, OR: 2.433; 95% CI: 1.161-5.100), and absent of extrathyroidal extension (p = 0.033, OR: 2.890; 95% CI: 1.052-7.940) were associated with RAS mutations. A significant association between BRAFV600E mutation and high clinical stage, tall-cell variants, non-encapsulated morphology, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis in PTC was observed. RAS mutations were associated with the follicular variant, encapsulated tumor, and no extrathyroidal extension. HRAS-mutated PTC frequently exhibited tumor multifocality.

MiR-495-3p regulates cell migration and invasion in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most prevalent histotype of thyroid cancer and the presence of BRAFV600E mutation in these tumors is related to the malignancy and prognosis of the disease. In recent years attention has been focused on the role of microRNAs in the biology of PTC cells, especially in their role in the modulation of pathways related to tumorigenesis. DLK1-DIO3-derived miRNAs have been shown to play important roles in tumor context and are globally downregulated in PTC. Based on a previous in silico target prediction and gene enrichment analysis, we identified miR-495-3p as the candidate with the highest tumor suppressor potential role in PTC among DLK1-DIO3-derived miRNAs. We used bioinformatics and an in vitro model of miR-495-3p overexpression to further understand the influence of this molecule on the tumorigenic processes of PTC. Overexpression of miR-495-3p impaired cell migration and invasion of PTC cells harboring the BRAFV600E mutation and affected the expression of targets predicted in the bioinformatic analysis, such as TGFB2, EREG and CCND1. Overall, our results indicate that the loss of miR-495-3p expression during PTC development might play an important role in its progression.

Predictive factors and risk analysis of recurrent laryngeal nerve invasion in papillary thyroid carcinoma ≤ 1 cm.

The recurrent laryngeal nerve (RLN) may be involved by papillary thyroid carcinoma ≤ 1 centimeter (PTC ≤ 1 cm). Current study investigated the predictive factors of RLN invasion in PTC ≤ 1 cm, the risk factors of disease recurrence in RLN invaded cases and the results of surgical management for RLN invasion. Data of 374 PTC ≤ 1 cm patients were retrospectively collected. We performed univariate and multivariate analysis to identify predictive factors of RLN invasion and risk factors of disease recurrence. The abilities of factors in predicting RLN invasion were evaluated. Surgical outcomes and recurrence free survival (RFS) of patients were analyzed. A total of 28 patients suffered RLN invasion, among which seven had disease recurrence. Preoperative vocal cord palsy (VCP), gross extrathyroidal extension, larger tumor size and tumor on the dorsal side of thyroid were verified as predictive factors of RLN invasion. RLN involved patients had poorer RFS, but better than those who also had upper-aerodigestive tract invasion. Upper-aerodigestive tract invasion, lateral neck lymph nodes metastasis (LNM) and BRAF V600E mutation were independent risk factors of disease recurrence in RLN invaded cases. Tumor shaving showed better RLN function preservation without increasing recurrent risk. Current study confirmed the rarity of RLN invasion in PTC ≤ 1 cm. Various aggressive features were verified as predictive factors of RLN invasion. Tumor shaving showed superiority in preserving nerve function without increasing recurrent risk. Special attentions should be paid for disease recurrence when RLN invasion accompanied by upper-aerodigestive tract invasion, lateral neck LNM or BRAF V600E mutation.

Retracted] MicroRNA‑509 targets PAX6 to inhibit cell proliferation and invasion in papillary thyroid carcinoma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that several of the panels shown for the cell invasion assays in Figs.2C and5D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 1403‑1409, 2019; DOI: 10.3892/mmr.2018.9750].

Role of Matrix Metalloproteinases and Their Inhibitors in Locally Invasive Papillary Thyroid Cancer.

Locally invasive papillary thyroid carcinoma (PTC) protrudes beyond the thyroid capsule and invades local structures. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in local invasion and metastasis in PTC. The aim of our study was to determine expression levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in tissue specimens of invasive and non-invasive PTC. Our hypothesis was that expression levels of these biomarkers correlate with the development of locally invasive PTC. In our single-center study we retrospectively investigated MMP and TIMP expression levels in 50 samples of thyroid tissue diagnosed as locally invasive papillary carcinoma (study group) and 30 samples of thyroid tissue diagnosed as non-invasive, non-metastatic papillary carcinoma (control group). Tissue specimens were immunohistochemically stained with primary monoclonal antibodies against MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2. When correlating expression levels of MMPs and TIMPs in thyroid tissue, statistically significant differences were found for MMP-1 and TIMP-1 expression (p &lt; 0.001; Mann-Whitney U test) with the highest levels of expression in the invasive PTC group. Although expression of MMP-9 and TIMP-2 was higher in invasive PTC, the differences were not statistically significant. Elevated expression of MMP-1 and TIMP-1 in tumor tissue can predict invasiveness for PTC.