Treatment Of Papillary Thyroid Carcinoma Research Articles

Extent of thyroid surgery for clinically node-negative papillary thyroid carcinoma with confirmed nodal metastases after prophylactic central neck dissection: a 15-year experience in a single center.

PurposeThe use of prophylactic central neck dissection (PCND) and the extent of thyroid surgery in clinically node-negative (cN0) papillary thyroid carcinoma (PTC) are controversial. This study aimed to investigate whether the extent of thyroid surgery influences the prognosis of patients with PTC with central lymph node metastasis (N1a), which was cN0 but pathologically confirmed after PCND.MethodsThis was a single-center retrospective study using medical records. Patients who underwent thyroid surgery with PCND for the treatment of PTC between 2004 and 2019 were included. Predictive factors and local recurrence rates were analyzed.ResultsOf 2,274 patients with cN0 PTC, 436 were confirmed to have pathologic N1a disease after PCND. Among them, 340 patients (78.0%) underwent total thyroidectomy (TT) and 96 patients (22.0%) underwent less than TT. Of the 374 patients who were followed up for >6 months, 5 (1.3%) experienced recurrence. The 15-year recurrence-free survival (RFS) rate was 98.2%. No clinicopathologic factor was predictive of tumor recurrence. RFS tended to be lower in patients who underwent less than TT than in those who underwent TT; however, the difference was not statistically significant.ConclusionOur study showed low recurrence rates in patients with cN0 PTC pathologically confirmed as N1a after PCND. The RFS did not differ according to the extent of thyroid surgery. Considering the low recurrence rate and the surgical morbidity associated with thyroid surgery, less than TT with PCND may be considered for patients with cN0 unilateral PTC even with a pathologic staging of N1a after PCND.

Analysis of patterns and risk factors regarding the onset of nodules in the contralateral thyroid lobe during follow-up ultrasonography among patients after unilateral lobectomy for the treatment of papillary thyroid carcinoma.

This study tries to find the patterns of new nodules in contralateral thyroid lobe among papillary thyroid carcinomas (PTCs) after lobectomy using ultrasonography. Of note, 456 PTCs were enrolled. Clinicopathological features of primary tumors and sonographic patterns of new nodules in contralateral lobe were documented. Logistic regression analysis was performed to identify risk factors for new nodules. The overall incidence of new nodules was 41.9%. 96.3% of new nodules were no greater than 1 cm while only 10.5% of those were with high suspicion of malignancy. There was no difference in the incidence and sonographic patterns of new nodules between patients with an original tumor size <1 cm (n = 267) vs 1 to 4 cm (n = 189). Multivariate logistic regression analysis showed age (OR, 1.021; 95% CI, 1.001-1.041; P = .036) played risk factor for new nodules while tumor size >1 cm did not. New nodules in the contralateral lobe were common, but usually small and benign by ultrasound features. Older age was found to be a risk factor to predict new nodules. This study supports lobectomy for 1-4 cm PTC in terms of incidence of new nodules on the remnant lobe.

Identification of key miRNAs in papillary thyroid carcinoma based on data mining and bioinformatics methods.

MicroRNAs (miRNAs) are a class of short (approximately 22 nucleotides), non-coding and endogenous RNA molecules that play pivotal roles in the occurrence and development of cancer. The present study aimed to investigate key miRNAs involved in papillary thyroid carcinoma (PTC). Two independent datasets (GSE73182 and GSE113629) were obtained from the GEO database. The differentially expressed miRNAs (DEmiRNAs) between PTC tissues and normal thyroid tissues were analyzed by GEO2R with the Limma R package. Key miRNAs in PTC were identified by the VennDiagram R package. The targets of the key miRNAs were predicted by miRWalk and were functionally enriched by clusterProfiler R package. Five miRNAs including hsa-miR-146b-5p, hsa-miR-15a-5p, hsa-miR-21-5p, hsa-miR-221-3p and hsa-miR-222-3p were identified as key miRNAs in PTC. The expression levels of these key miRNAs were upregulated in PTC. This finding was also confirmed in the other dataset. Target prediction of miRNAs indicated that hsa-miR-146b-5p, hsa-miR-15a-5p, hsa-miR-21-5p, hsa-miR-221-3p and hsa-miR-222-3p exhibited 2, 41, 3, 14 and 8 target genes, respectively. Enrichment analysis indicated that these key miRNAs were mainly involved in nine biological processes, such as regulation of MAP kinase activity, JNK cascade signaling and regulation of protein serine/threonine kinase activity) and in 28 pathways, including the mitogen associated protein kinase, the sphingolipid, ErbB, Ras and the C-type lectin receptor signaling pathways. In conclusion, the present study identified several key miRNAs in PTC, which serve as potential targets for PTC diagnosis and treatment.

Upregulation of microRNA-143-3p induces apoptosis and suppresses proliferation, invasion, and migration of papillary thyroid carcinoma cells by targeting MSI2

As a tumor-associated biological molecule, microRNA-143-3p (miR-143-3p) is implicated in the progression of papillary thyroid carcinoma (PTC). We conducted this study to elucidate the effects of miR-143-3p mediated by Musashi RNA binding protein 2 (MSI2) on the biological activities of PTC cells. The K1 cells with the lowest miR-143-3p expression were selected for the experiments. The targeting relationship between miR-143-3p and MSI2 was verified. The biological functions of miR-143-3p and MSI2 with respect to K1 cell proliferation, cycle distribution, apoptosis, invasion, migration, and tumorigenesis were studied using gain- and loss-of-function assays both in vitro and in vivo. MSI2 was verified to be a target gene of miR-143-3p. Cells treated with upregulation of miR-143-3p or silencing of MSI2 exhibited significantly decreased the expression of Bcl-2, PCNA, MCM2, Ki67, MSI2, MMP-2, and MMP-9. This was accompanied by inhibited cell proliferation, cell invasion, and migration, as well as a significant increase in Bax expression, cell cycle arrest, and cell apoptosis. More importantly, the tumor inhibitory effects of upregulated miR-143-3p were also confirmed in the tumor xenografts in nude mice. Our results indicate that upregulation of miR-143-3p suppresses the progression of PTC by impeding cell growth, invasion, and migration via downregulation of MSI2, highlighting the potential of miR-143-3p as a target for future PTC treatment.

EZH2 upregulation by ER\u03b1 induces proliferation and migration of papillary thyroid carcinoma

BackgroundThe incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide in recent years. Therefore, novel potential therapeutic targets for PTC are urgently needed. Enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to PRC2, plays important roles in epigenetic silencing and cell cycle regulation. EZH2 overexpression has been found in several malignant tumor tissues, while its expression and function in PTC are largely unknown.MethodsSixty-five cases of PTC tissue confirmed by pathology and 30 cases of normal thyroid tissue adjacent to PTC tissue were collected from patients undergoing surgical treatment, between February 2003 and February 2006. We investigated the clinic pathologic significance of EZH2 expression using Realtime-PCR and IHC in 65 human PTC tissues and 30 normal thyroid tissue samples. The EZH2 expression in human PTC cell lines (K1 and W3) and the normal thyroid follicular epithelial cell line Nthy-ori 3–1 was analyzed by Western blotting and Realtime PCR. The expressions of ERα and ERβ in cell lines were analyzed by Realtime PCR.The tumor cell biological behavior was evaluated by CCK8 assay, colony formation assay, transwell migration assay and xenograft tumors model.ResultsHigher rate of EZH2 expression was found in PTC tissues than in normal thyroid tissues, EZH2 expression is associated with lymph node metastasis and recurrent. Inhibition of EZH2 in PTC cell lines downregulates cellular proliferation and migration. PTC is a disease with high incidence of female and E2-ERα upregulates EZH2 expression.ConclusionsThese results suggest a potential role of EZH2 for the PTC growth and metastasis. As a novel therapy, a pharmacological therapy targeting EZH2 has full potential in treatment of PTC.

Next-generation sequencing identified somatic alterations that may underlie the etiology of Chinese papillary thyroid carcinoma.

To better understand the etiology of papillary thyroid carcinoma, we did next-generation sequencing for the exomes and transcriptomes of a Chinese cohort of 28 pairs of DNA and RNA samples extracted from papillary thyroid carcinoma tumors and adjacent normal thyroid samples. The Chinese papillary thyroid carcinoma tumors harbored somatic mutations in the known driver genes, such as KRAS, TP53, BRAF, ERBB2 , and MET . In addition, we identified novel papillary thyroid carcinoma candidate genes that had not been well studied before. We also identified a gene mutation signature involving SPTA1, MAP2, SYNE1 , and SLIT3 that is significantly associated with survival of papillary thyroid carcinoma patients. Transcriptome analysis using the initial papillary thyroid carcinoma tumor samples and a new Chinese papillary thyroid carcinoma dataset identified six commonly upregulated oncogenic pathways in both datasets including eukaryotic translation initiation factor 2, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/serine/threonine kinase (AKT), Ephrin Receptor, Rho Family GTPase signaling, nuclear factor, erythroid 2 like 2 (NRF2)-mediated oxidative stress response, and remodeling of epithelial adherens junctions. Overall, we identified novel candidate genes and oncogenic pathways important to the etiology of papillary thyroid carcinoma in Chinese patients and found the association of a gene signature with the survival outcome of the thyroid cancer patients. These findings may help in moving toward the more comprehensive and effective personalized treatment of papillary thyroid carcinoma in Chinese.

Treatment of Papillary Thyroid Carcinoma With Radiofrequency Ablation

Treatment of Papillary Thyroid Carcinoma With Radiofrequency Ablation

The Transareola Endoscopic Approach Yields Adequate Oncological Dissection as Open Approach in the Treatment of Papillary Thyroid Carcinoma.

This study aimed to evaluate and discuss whether the transareola endoscopic surgery has similar outcome outcomes to open surgery in the treatment of papillary thyroid carcinoma (PTC). A total of 102 patients with PTC were enrolled in this study. Among them, 53 patients were treated by transareola endoscopic surgery (endoscopic group) and 49 patients were treated by open surgery (open group). Some specific factors, including thyroglobulin (Tg), radioactive iodine uptake (RAIU), postoperative nuclide imaging in thyroid area, postoperative nuclide imaging of lymph nodes suspicious for metastasis (PNILNSM), etc. were analyzed and compared between the 2 groups. There were no significant differences between the 2 groups regarding body mass index (22.9±3.4 vs. 24.0±3.3, P=0.103), operation time (173.3±43.2 vs. 158.8±47.9 min, P=0.110), intraoperative blood loss (41.8±19.4 vs. 35.8±31.0 mL, P=0.251, P=0.251), tumor diameter (19.0±6.8 vs. 20.2±7.2 mm, P=0.400), and overall complications (11.3% vs. 10.2%, P=0.868). No significant difference was found in the specific factors between the 2 groups concerning RAIU-2h/24h (2.44±1.34 vs. 2.58±1.65%/2.83±3.75 vs. 2.35±3.44%, P=0.646/ P=0.506), number of dissected lymph nodes (4.4±1.4 vs. 4.6±1.5, P=0.595), Tg before radioiodine therapy (4.46±5.50 vs. 5.60±8.36; P=0.495), Tg after radioiodine therapy (1.03±1.93 vs. 1.11±1.61, P=0.812, P=0.812), postoperative nuclide imaging in thyroid area (1.76±1.50 vs. 2.19±1.85 cm, P=0.195), PNILNSM before radioiodine (none: 79.2% vs. 83.7%, P=0.566; central: 17.0% vs. 12.2%, P=0.653; lateral: 1.9% vs. 4.1%, P=0.450; central+lateral: 1.9% vs. 0%, P=1.000), and PNILNSM after radioiodine (none: 94.3% vs. 95.9%, P=0.111; central: 3.8% vs. 2.0%, P=1.000; lateral: 0 vs. 2.0%, P=0.480; central+lateral: 1.9% vs. 0%, P=1.000). Transareola endoscopic total thyroidectomy and central lymph nodes dissection are safe and effective. According to the evaluated postoperative specific factors, this technique achieves similar outcomes to open surgery in selected patients with PTC.

MicroRNA-486 inhibits cell proliferation, invasion and migration via down-regulating the TENM1 expressions and affecting ERK and Akt signaling pathways and epithelial-to-mesenchymal transition in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is one of the general thyroid malignancies. Recently, microRNAs (miRNAs) have identified as pivotal gene regulators in PTC tumorigenesis. The aim of this study was to investigate the role of miR-486 in PTC and its underlying mechanism. Fifty-six pairs of PTC tissue and matched normal tissue samples were collected from PTC patients who underwent surgery at our hospital from March 2015 to September 2017. Human thyroid epithelial cell line Nthy-ori3-1and PTC cell lines (BCPAP, K1, HTH83, and TPC-1) were cultured. The mRNA and protein expression level were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Additionally, the proliferation and migration abilities were checked by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method and transwell assay, respectively. Furthermore, dual-luciferase reporter assay was performed to confirm the combination of miR-486 and TENM1. Xenograft Model experiments were performed to assess the effects of miR-486 on tumor growth in vivo. MiR-486 expression was significantly reduced in PTC, which was associated with the poorer clinicopathologic characteristics and overall survival (OS) of PTC patients. Moreover, miR-486 restoration in PTC cells was confirmed to markedly inhibit proliferation, invasion, and migration via the regulation of extracellular-signal-regulated kinase (ERK) and protein kinase B (Akt) signaling pathways and epithelial-mesenchymal transition (EMT). In the meantime, teneurin transmembrane protein 1 (TENM1) was identified as a direct functional target for miR-486 in PTC cells on the basis of bioinformatic analysis and luciferase reporter assays. Additionally, we also verified that miR-486 restoration could prominently repress the PTC growth in vivo. MiR-486 exerted anti-tumor functions in PTC progression and served as promising biomarkers for the PTC treatment.

MicroRNA-599 promotes apoptosis and represses proliferation and epithelial-mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2-depentent Notch signaling pathway.

Although papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA-599 (miR-599) on proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual-luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR-599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR-559. In addition, the expression of Bax and E-cadherin was elevated while that of Hey2, Notch1, Delta-like1, Hes1, N1ICD, Jagged1, Snail, Slug, N-cadherin and Vimentin, and Bcl-2 was reduced in cells treated with upregulated miR-599 or downregulated Hey2. Moreover, miR-599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR-599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.

Identification and Validation of Core Genes Involved in the Development of Papillary Thyroid Carcinoma via Bioinformatics Analysis.

Background Papillary thyroid carcinoma (PTC) is a common endocrine malignant neoplasm, and its incidence increases continuously worldwide in the recent years. However, efficient clinical biomarkers were still deficient; the present research is aimed at exploring significant core genes of PTC. Methods We integrated three cohorts to identify hub genes and pathways associated with PTC by comprehensive bioinformatics analysis. Expression profiles GSE33630, GSE35570, and GSE60542, including 114 PTC tissues and 126 normal tissues, were enrolled in this research. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were utilized to search for the crucial biological behaviors and pathways involved in PTC carcinogenesis. Protein-protein interaction (PPI) network was constructed, and significant modules were deeply studied. Results A total of 831 differentially expressed genes (DEGs) were discovered, comprising 410 upregulated and 421 downregulated genes in PTC tissues compared to normal thyroid tissues. PPI network analysis demonstrated the interactions between those DEGs, and top 10 pivotal genes (TGFB1, CXCL8, LRRK2, CD44, CCND1, JUN, DCN, BCL2, ACACB, and CXCL12) with highest degree of connectivity were extracted from the network and verified by TCGA dataset and RT-PCR experiment of PTC samples. Four of the hub genes (CXCL8, DCN, BCL2, and ACACB) were linked to the prognosis of PTC patients and considered as clinically relevant core genes via survival analysis. Conclusion In conclusion, we propose a series of key genes associated with PTC development and these genes could serve as the diagnostic biomarkers or therapeutic targets in the future treatment for PTC.

Sevoflurane inhibits the progression of PTC by downregulating miR-155.

Surgery resection is the primary treatment for papillary thyroid carcinoma (PTC) patients with the risk of tumor cell invasion and distant metastasis. Sevoflurane is a volatile anesthetic agent widely used in clinical applications. However, the effect of sevoflurane on PTC cells and its precise mechanism remain largely unknown. Cell viability was assessed by MTT assay. The migrative and invasive abilities of the cells were measured by transwell assay. The protein expression level of Bax, Bcl-2, MMP 9, and MMP 2 were detected by Western blot. Cell apoptosis was analyzed by flow cytometry. The qRT-PCR analysis was used to determine miR-155 expressions. Sevoflurane greatly decreased the viability of PTC cells in a dose-dependent manner. Moreover, sevoflurane significantly inhibited migration and invasion, but increased the apoptosis in PTC cells, which could be reversed by the addition of miR-155. Besides, sevoflurane evidently increased the Bax protein level and inhibited the protein level of Bcl-2, MMP9, and MPP2 in PTC cells. In addition, miR-155 was upregulated in PTC cells; however, the amount of miR-155 would be decreased in PTC cells treated with sevoflurane. Furthermore, abrogation of miR-155 promoted cell apoptosis and inhibited cell migration and invasion in PTC cells. Sevoflurane inhibited migration and invasion, while enhanced cell apoptosis by downregulating miR-155 in PTC cells, suggesting important clinical implications for anesthetic agents to prevent the metastasis in PTC.

MiRNA-15a regulates the proliferation and apoptosis of papillary thyroid carcinoma via regulating AKT pathway.

AimAberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. The expression of miR-15a was reported to be downregulated in papillary thyroid carcinoma (PTC) compared to control tissue. However, the mechanism underlying this downregulation remains unclear.MethodsThe effects of miR-15a on the proliferation and invasion of PTC cells were evaluated by CCK-8 and transwell assays, respectively. Expression levels of AKT and rearranged during transfection (RET) in cells were assessed using Western blotting. The correlation of RET and miR-15a was validated by luciferase reporter assay. Moreover, in vivo assay was performed to demonstrate the effect of miR-15a on tumor growth.ResultsWe confirmed that the expression of miR-15a was significantly lower in PTC tissue than that in normal tissue. Overexpression of miR-15a notably inhibited PTC cell proliferation and invasion via promoting apoptosis. Additionally, RET was found to be a target of miR-15a and this correlation was confirmed by dual-luciferase assay and Western blot. Furthermore, in vivo study revealed that overexpression of miR-15a inhibited tumor growth via downregulating the levels of RET and phosphorylated AKT.ConclusionIn the present study, we demonstrated that miR-15a played an antitumor role in regulating PTC via targeting RET/AKT pathway. Therefore, miR-15a may serve as a potential molecular target for the treatment of PTC.

Comparison of transoral endoscopic thyroidectomy vestibular approach, total endoscopic thyroidectomy via areola approach, and conventional open thyroidectomy: a retrospective analysis of safety, trauma, and feasibility of central neck dissection in the treatment of papillary thyroid carcinoma.

Transoral endoscopic thyroidectomy vestibular approach (TOETVA) and total endoscopic thyroidectomy via areola approach (ETA) are commonly used endoscopic thyroidectomy approaches. This study compares the effectiveness of these approaches with conventional open thyroidectomy (COT) in terms of safety, associated trauma, and feasibility of central neck dissection in the treatment of papillary thyroid carcinoma (PTC). This retrospective study included patients who underwent TOETVA (n = 100), ETA (n = 119), and COT (n = 289). All patients had a pathological diagnosis of PTC and underwent unilateral lobectomy and central neck dissection. We analyzed operative time, postoperative drainage volume, postoperative C-reactive protein (CRP), preoperative and postoperative white blood cell (WBC) count and parathyroid hormone (PTH) levels, parathyroid damage, hoarseness, total number of central lymph nodes, and number of metastatic central lymph nodes. The clinical characteristics across the three groups were similar except for patient sex and age. There was a higher proportion of young women in the TOETVA and ETA groups than in the COT group. There were significant differences between the three groups regarding operative time (P = 0.000), postoperative drainage volume (P = 0.000), postoperative CRP (P = 0.000), ∆WBC (P = 0.000), and length of postoperative hospital stay (P = 0.021); in the TOETVA and ETA groups, operative time (P = 0.445), postoperative drainage volume (P = 0.677), and length of postoperative hospital stay (P = 0.145) were not significantly different. The percentage of cases with parathyroid gland damage (P = 0.459) and hoarseness (P > 0.05) was similar in all groups. All three procedures were efficient in performing a central lymph node dissection. Although considered more traumatic, TOETVA and ETA are both safe treatment options for PTC. They can both achieve similar therapeutic effects of central neck dissection in the treatment of PTC when compared with open surgery.

Integrated analysis identifying new lncRNA markers revealed in ceRNA network for tumor recurrence in papillary thyroid carcinoma and build of nomogram.

The risk of tumor recurrence is currently the focus of clinical attention in the treatment of papillary thyroid carcinoma (PTC). This study focuses on the identification of novel prognostic long noncoding RNA (lncRNA) signatures for tumor recurrence in PTC. RNA sequencing profiling of patients with PTC was obtained from the TCGA and Gene Expression Omnibus databases. Differently expressed lncRNA, microRNA (miRNA), and messenger RNA (mRNA) signatures between patients with and without tumor recurrence were selected. The lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network for tumor recurrence in PTC was constructed to identify lncRNAs associated with tumor relapse in papillary carcinoma. Functional enrichment analysis was performed. Adjusted odds ratios were estimated to identify candidate prognostic lncRNAs considering clinical covariates. Validation analysis was conducted. Nomogram was built based on the verified prognostic lncRNAs and clinical features. The lncRNA-miRNA-mRNA ceRNA network for tumor recurrence in PTC was constructed. Functional enrichment analysis suggested that the identified lncRNAs were associated with PTC. Adjusted odds ratios indicated that 5 of the 16 selected lncRNAs were candidate biomarkers predicting tumor recurrence of thyroid carcinoma. Among which, TTTY10 was verified as novel prognostic markers in validation analysis. Nomogram was built based on the newly identified lncRNA biomarker and clinical covariates. In this study, lncRNA TTTY10 was identified as potential novel prognostic markers predicting tumor recurrence in PTC. It may provide useful information for future molecular and cohort studies focusing on the prognosis of PTC.

The impact of completion thyroidectomy followed by radioactive iodine ablation for patients with lymph node recurrence of papillary thyroid carcinoma

BackgroundAlthough lobectomy is considered acceptable as a primary surgical treatment for papillary thyroid carcinoma in properly selected patients, a standard treatment for postlobectomy lymph node recurrence has not been established. Here we compared the effectiveness of therapy with lymphadenectomy alone to that of treatment with completion thyroidectomy and lymphadenectomy followed by radioactive iodine. MethodsThis was a retrospective study of patients with papillary thyroid carcinoma who underwent surgery for lymph node recurrence in the period from January 2003 to December 2008, all of whom had previously undergone initial lobectomy with or without lymph node dissection. One-hundred and twenty-five patients were included in the primary analysis. ResultsNinety-eight of these patients underwent lymphadenectomy alone (L group), and 27 received lymphadenectomy and completion thyroidectomy followed by radioactive iodine (LC&R group). The median follow-up time was 10.2 years. The overall survival, distant relapse-free survival, and lymph node relapse-free survival were not significantly different between the LC&R and L groups (P = .89, 0.58, and .22, respectively), whereas the LC&R group patients had significantly longer operation time, higher blood loss, and a higher rate of postoperative hypoparathyroidism compared with the L group (P < .001, respectively). ConclusionCompared with completion thyroidectomy and lymphadenectomy followed by radioactive iodine, lymphadenectomy alone was considered an acceptable therapeutic option which decreased the surgical disadvantages but did not decrease survival for at least 10 years after recurrence surgery for PTC patients with only lymph node recurrence.

Silencing of long noncoding RNA RP11-476D10.1 enhances apoptosis and autophagy while inhibiting proliferation of papillary thyroid carcinoma cells via microRNA-138-5p-dependent inhibition of LRRK2.

The distant metastasis in papillary thyroid carcinoma (PTC) is a major threat for PTC patients. Moreover, the involvement of long noncoding RNAs (lncRNAs) in the regulation of PTC progression has been extensively investigated. The aim of this study was to underscore whether lncRNA RP11-476D10.1 affects the proliferation, apoptosis and autophagy of PTC cells. Initially, we determined that lncRNA RP11-476D10.1 and LRRK2 were highly expressed in PTC cells. Meanwhile, through experimentation, miR-138-5p was confirmed to bind with lncRNA RP11-476D10.1 and LRRK2. It was also revealed that lncRNA RP11-476D10.1 downregulated the miR-138-5p expression, thereby upregulating the LRRK2 expression. After that, PTC cells were transfected with siRNA against RP11-476D10.1, or inhibitor or mimic of miR-138-5p to evaluate the influence of lncRNA RP11-476D10.1 on the PTC cell proliferation, apoptosis, and autophagy in vitro and on the tumor formation ability in vivo. The results showed that silenced lncRNA RP11-476D10.1 or overexpressed miR-138-5p enhanced the apoptosis and autophagy of PTC cells while reducing cell proliferation, with increased levels of Bax, LC3B, and Beclin1 and decreased Bcl-2 level were observed. The inhibitory role of silenced lncRNA RP11-476D10.1 role in the PTC development was further verified by the reduced tumor formation ability in nude mice. Our results demonstrated that lncRNA RP11-476D10.1 could bind to miR-138-5p and promote LRRK2 expression. Moreover, the silencing of lncRNA RP11-476D10.1 may inhibit the development of PTC, highlighting a novel insight for the development of superior therapeutic targets for PTC treatment.

Clinical analysis of transthoracic and mammary minimally invasive endoscopic surgery in the treatment of papillary thyroid carcinoma

Objective To investigate the clinical effect of transthoracic and mammary minimally invasive endoscopic surgery in the treatment of papillary thyroid carcinoma. Methods Forward-looking inclusion 186 patients of papillary thyroid carcinoma in our hospital from August 2016 to June 2018, there were 113 males and 73 females.All the patients were divided into two groups at random by using SPSS 17.0 software, which were numbered 1 to 186 in sequence, and the patients were divided into two groups at random.Among them, 105 cases were underwent transthoracic and mammary minimally invasive endoscopic surgery (observation group), 81 cases were underwent open operation (control group). Compared the three groups of patients with operation time, intraoperative blood loss, postoperative cervical autonomic activity time, postoperative hospital stay, postoperative pain score on the first day and postoperative complications and so on. The measured data were expressed by t test of group design data, the counting data were expressed by χ2 test. Results There was no perioperative deaths and serious complications during perioperative in this two groups. No transmissible open operation was found in the observation group. The difference was not statistically significant in operation time and intraoperative blood loss between this two groups, [(55.83±4.52) min vs (56.72±6.28)min, t=3.158, P=0.284; (24.65±8.13) ml vs (25.83±7.42) ml, t=4.146, P=0.173]. The observation group was superior to the control group in postoperative cervical autonomic activity time, postoperative hospital stay and postoperative pain score on the first day [(1.58±0.24) d vs (2.77±0.61) d, t=7.355, P=0.020; (4.33±1.04) d vs (6.75±1.81) d, t=6.814, P=0.031; (2.15±0.71) scores vs (4.34±1.03) scores, t=6.923, P=0.026]. There was no significant difference in postoperative complications(incisional infection, hypocalcemia, drinking water choking, hoarseness) between the two groups (χ2=1.674, P=0.643). The median follow-up was 10 months(monthly follow-up by telephone) and no recurrence occurred during the follow-up. Conclusion Transthoracic and mammary minimally invasive endoscopic surgery in the treatment of papillary thyroid carcinoma has the advantages of small trauma, quick recovery and high aesthetic value, which is worthy of clinical promotion. Key words: Thoracoscopes; Thyroid gland; Carcinoma, papillary

Identifying gene modules of thyroid cancer associated with pathological stage by weighted gene co-expression network analysis

Thyroid cancer is the most common type of endocrine tumor. The TNM classification remains a standard for treatment determination and predicting prognosis in thyroid cancer. The genes modules associated with the progression of papillary thyroid carcinoma (PTC) were not clear. We applied a weighted gene co-expression network analysis (WGCNA) and differential expression analysis to systematically identified co-expressed gene modules and hub genes associated with PTC progression based on The Cancer Genome Atlas (TCGA) PTC transcriptome sequencing data. An independent validation cohort, GSE27155, was used to evaluate the preservation of gene modules. We identified two co-expressed genes modules associated with progression of PTC. Enrichment analysis indicated that the two modules were enriched in angiogenesis and extracellular matrix organization. DCN, COL1A1, COL1A2, COL5A2 and COL3A1 were hub genes in the co-expressed network. We systematically identified co-expressed gene modules and hub genes associated with PTC progression for the first time, which provided insights into the mechanisms underlying PTC progression and some potential targets for the treatment of PTC.

Microarray-based differential expression profiling of long noncoding RNAs and messenger RNAs in formalin-fixed paraffin-embedded human papillary thyroid carcinoma samples.

BackgroundLong noncoding RNAs (lncRNAs) can regulate the expression of genes at almost every level. The altered expression of lncRNAs was observed in many kinds of cancers. Until recently, few studies have focused on the function of lncRNAs in the context of papillary thyroid carcinoma (PTC).MethodsIn the current study, we collected seven PTC and nodular goiter tissue samples and explored mRNA and lncRNA expression patterns in these samples by microarray.ResultsWe observed aberrant expression of 94 lncRNAs and 99 mRNAs in the seven PTC samples as compared to the nodular goiter tissue [fold change (FC) ≥2.0; P<0.01]. To confirm these microarray results, quantitative polymerase chain reaction (q-PCR) was performed to assess the expression of three randomly selected differentially expressed mRNAs and lncRNAs, confirming our microarray findings significantly. We then performed gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses to systematically characterize the twelve significantly differential genes. A co-expression analysis revealed that the lncRNAs n382996, n342483, and n409114 were closely related to the regulation of MT1G, MT1H, and MT1F.ConclusionsIn the present study a string of novel lncRNAs associated with PTC were identified. Further study of these lncRNAs should be performed to identify novel target molecules which may improve diagnosis and treatment of PTC.