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Lymph node metastasis can independently predict oral squamous cell carcinoma patients' survival. This study would investigate the genetic and cellular differences between oral squamous cell carcinoma with positive and negative lymph node metastases.We gathered single-cell RNA sequencing and bulk gene expression data from the Cancer Genome Atlas and Gene Expression Omnibus databases. Sixty lymph node-metastasis-related genes were discovered with refined single-cell RNA sequencing data analysis, and consensus clustering provided three molecular subtypes of oral squamous cell carcinoma. Least absolute shrinkage and selection operator analyses were then utilized to establish a five-gene risk model. CIBERSORT analysis revealed the immune infiltration profile of different risk subgroups.Oral squamous cell carcinoma patients were classified into three subtypes based on the 60 lymph node-metastasis-related key genes identified by single-cell RNA sequencing data. Patients in Subtype 3 showed a tendency for lymph node metastasis and poorer prognosis. Moreover, five biomarkers were selected from the 60 genes to construct a five-gene risk model evaluating the risk of lymph node metastasis. A lower probability of lymph node metastasis and a better prognosis was observed in the low-risk group. The immune infiltration of three different risk groups was explored with CIBERSORT. Besides, further analysis implied different sensitivities of anticancer drugs, including immunotherapy drugs and targeted compounds, in the three risk groups.In view of intratumoral heterogeneity, we found 60 genes associated with lymph node metastasis of oral squamous cell carcinoma. Subsequently, we constructed a five-gene signature that could improve the prediction of lymph node metastasis, clinical outcome, and promote individualized treatment strategies for oral squamous cell carcinoma.

The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications., The characterisation of the papillary thyroid carcinoma (PTC) tumour microenvironment remains crucial. Here, the authors perform single-cell RNA sequencing in 11 patients and identify potential opportunities for the use of immunotherapy and its combination with anti-angiogenic therapy in PTC.

The objective of this study is to demonstrate a novel method for the reconstruction of right recurrent laryngeal nerve (RLN) by transforming into nonrecurrent RLN: the end-to-free vagal laryngeal branch end anastomosis. Here we report a case of locally advanced thyroid carcinoma. The patient underwent radical thyroid surgery with inevitably partial RLN resection and immediate right RLN reconstruction at our institution. With the guidance of intraoperative neuromonitoring (IOMN), we completed a novel end-to-free vagal laryngeal branch end anastomosis. The whole procedure was deliberately monitored by IOMN. Surgeons can procure adequate free nerve for tension-free anastomosis by transforming the right RLN into nonrecurrent nerve. Follow-up laryngoscope showed improved adductory movement of the right arytenoid. The end-to-free vagal end anastomosis is an effective way to reconstruct segmental nerve resection of right RLN. Its long-term postoperative result needs to be further warranted.

Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its c...

The coexistence of BRAF V600E and the telomerase reverse transcriptase (TERT) promoter mutation C228T/C250T is extensively associated with thyroid cancer prognosis. Our study aimed to establish a sensitive method for mutation detection and explore the correlation in detail.The BRAF and TERT promoter mutation status of 250 papillary thyroid cancers was determined using amplification-refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) and Sanger sequencing to compare the sensitivity of the 2 methods. Associations between the mutation status and clinicopathological features were then analyzed.ARMS-qPCR was more sensitive than Sanger sequencing (BRAF V600E: 75.2% [188 of 250] vs 52.4% [131 of 250], P.001; TERT promoter C228T/C250T mutation: 12.0% [30 of 250] vs 3.6% [9 of 250], P = .001; comutation: 9.6% [24 of 250] vs 3.2% [8 of 250], P = .005). Both ARMS-qPCR and Sanger sequencing indicated that patients with coexisting BRAF V600E and TERT promoter mutations had an older diagnosis age, higher recurrence rate, and were associated with a more advanced TNM stage and higher metastasis, age, completeness of resection, invasion, and size score. Moreover, ARMS-qPCR helped identify an earlier group stage, which was younger and had smaller tumors and a lower recurrence rate, compared with the group with coexisting BRAF V600E and TERT promoter mutations identified by Sanger sequencing. The newly identified group had a lower metastasis, age, completeness of resection, invasion, and size score and TNM stage.Patients with coexisting BRAF V600E and TERT promoter mutations had a worse prognosis. ARMS-qPCR, the more sensitive method, can be used to identify patients who have a potentially worse prognosis earlier.

ContextProgrammed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin and ITIM domain (TIGIT) are considered major immune co-inhibitory receptors (CIRs) and the most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in medullary thyroid carcinoma (MTC).ObjectiveWe aimed to provide the first evidence regarding the expression profiles and clinical significance of CIRs in a large cohort of MTC patients.Design and PatientsIn total, 200 MTC patients who received initial surgery in our hospital were included. Immunohistochemistry was performed to evaluate CIR expressions in tissue microarrays (TMAs). Combined with the results of our previous programmed cell death ligand-1 (PD-L1) study, clinicopathologic and prognostic correlations of these proteins were retrospectively analyzed.ResultsTIM-3, PD-1, CTLA-4, LAG-3, and TIGIT positivity was detected in 96 (48.0%), 27 (13.5%), 25 (12.5%), 6 (3.0%), and 6 (3.0%) patients, respectively, in whom TIM-3, PD-1, and CTLA-4 expressions were positively correlated. Log-rank tests and multivariate Cox analyses both indicated that TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression were associated with worse structural recurrence-free survival. In addition, among 20 patients who developed advanced disease during follow-up, 12 (60%) showed TIM-3 positivity, among whom 6 cases also had concurrent moderate to strong PD-1, PD-L1, or CTLA-4 expression.ConclusionsUsing the currently largest TMA cohort of this rare cancer, we delineated the CIR expression profiles in MTC, and identified TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression as promising biomarkers for tumor recurrence. Furthermore, a subset of advanced MTCs are probably immunogenic, for which single or combined immunotherapy including TIM-3, PD-1, PD-L1, or CTLA-4 blockade may be potential therapeutic approaches in the future.

BCOR-rearranged sarcoma is the third common subtype of undifferentiated small round cell sarcoma and was first recognized in 2012 from bone sarcoma with a similar morphological manifestation with undifferentiated round cell but totally different molecular hallmark from Ewing sarcoma. Primary BCOR-rearranged sarcomas were mostly found in bone and soft tissue and were sporadically reported in viscera involving kidney, which add difficulties in differential diagnosis. Here we present a 21 years old male patient with BCOR-CCNB3 in neck, which first diagnosed as thyroid cancer.

Forcher and Contributor ID) account on MTS. To register a linked ORCID account, please go to the Account Update page (http://mts.hindawi.com/update/) in our Manuscript Tracking System and after you have logged in click on the ORCID link at the top of the page. This link will take you to the ORCID website where you will be able to create an account for yourself. Once you have done so, your new ORCID will be saved in our Manuscript Tracking System automatically."?> the rare but aggressive insular thyroid carcinoma (ITC), there's no clear evidence to determine whether prophylactic central compartment neck dissection (CCND) is necessary for cN0 disease. This study provides the first evidence that treating cN0 ITC without prophylactic CCND is associated with decreased survival regardless of T staging and administration of RAI therapy. Background. Regarding the rare but aggressive insular thyroid carcinoma (ITC), the value of prophylactic central compartment neck dissection (CCND) for clinically node-negative (cN0) disease is unclear. We aimed to provide the first evidence. Methods. N0 and pN1a ITC patients were identified from the Surveillance, Epidemiology, and End Results database. These patients were divided into thyroid-surgery + CCND group (pN0/pN1a patients confirmed by CCND) and thyroid-surgery group (cN0 patients without CCND). Differences in overall survival (OS) and disease-specific survival (DSS) between the two groups were evaluated. Subgroup analyses were also conducted. Results. Of the overall 112 patients, 44 (39.3%) received CCND. On multivariate analyses, the lobectomy ± isthmusectomy/total-thyroidectomy (Lob/TT) group demonstrated poorer OS and DSS than the Lob/TT + CCND group (P<0.05). When we separately analyzed patients treated by TT, multivariate analyses showed the TT group still revealed compromised OS and DSS than the TT + CCND group (P<0.05). Furthermore, absence of CCND independently predicted decreased OS no matter whether radioactive iodine (RAI) was administered. Similar results were obtained for T3/T4 patients. Moreover, for T1/T2 patients receiving CCND, 0/12 died during the study period, while for T1/T2 patients without CCND, 8/23 (34.8%) died, 5/23 (21.7%) due to ITC. Conclusion. Regardless of T staging and RAI treatment, cN0-ITC patients without CCND had decreased survival compared with pN0/pN1a patients receiving CCND. Therefore, if a cN0 patient is diagnosed with ITC, prophylactic CCND may be considered as a secondary procedure (postoperatively diagnosed) or a primary procedure (preoperatively/intraoperatively diagnosed). Prospective studies are expected to validate the conclusion.

Background Patients with anaplastic thyroid cancer (ATC), which is among the deadliest of all cancers, often have a poor response to traditional therapies. Currently, the role of long non-coding RNAs (lncRNAs) in ATC carcinogenesis is unclear. In this study, we analyzed the lncRNA expression profile of ATC with the aim of identifying potential molecular targets for treatment of the disease. Methods Whole transcriptome sequencing of three ATC and two normal thyroid (NT) samples was performed, and the lncRNA expression profile of ATC was analyzed. Original data as well as datasets deposited in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used for clinical validation. Cell proliferation, Transwell, and apoptosis assays were performed using ATC cell lines. Gene Ontology (GO) and gene set enrichment analyses (GSEA) were performed to determine the dysregulated pathways. Results Whole transcriptome sequencing revealed 182 lncRNAs to be differentially expressed in ATC. One of the lncRNAs, mitotically associated long non-coding RNA (MANCR; LINC00704), was significantly overexpressed in ATC cell lines and patient samples compared with NT and papillary thyroid cancer (PTC). MANCR depletion in ATC cells significantly inhibited cancer cell proliferation and invasion, and induced apoptosis. By further analyzing the transcriptome data, we identified 451 genes co-expressed with MANCR. GO and GSEA showed that the top dysregulated pathways were related to mitosis and cell cycle. Conclusions MANCR is a tumor promoter in ATC, and its role in carcinogenesis is possibly associated with cell cycle regulation. Because MANCR expression is minimal in most normal tissues, it may serve as a potential target in the future treatment of ATC.

6588 Background: Co-existing of BRAF V600E and TERT promoter C228T/C250T mutation has been extensively related to prognosis in thyroid cancer. Our study aimed to establish a more sensitive method for mutation detection and explore the correlation more in-depth. Methods: BRAF and TERT promoter mutation status of 250 papillary thyroid cancer was detected by both Amplification Refractory Mutation System quantitative PCR (ARMS-qPCR) and Sanger sequencing to compare the sensitivity. The associations between the mutation status and the clinicopathological features were analyzed. Results: ARMS-qPCR displayed higher sensitivity than Sanger ( BRAF V600E: 75.2% vs. 52.4%, p< 0.001; TERT promoter C228T/C250T: 12.0% vs. 3.6%, p= 0.001; Co-mutation (9.6% vs. 3.2%, p= 0.005). Both methods indicated that patients with BRAF V600E and TERT promoter co-mutation were higher in age at diagnosis (ARMS-qPCR: 51.0 ± 14.2 vs. 40.2 ± 12.6, p

Desoxyrhapontigenin (DRG, 4-methoxyresveratrol or trans-3,5-dihydroxy-4'-methoxystilbene) is a naturally occurring resveratrol (RES) derivative with a variety of biological activities. To facilitate its further medicinal exploration, a reliable LC-MS/MS method was developed and validated for the quantification of DRG in rat plasma using heavy isotope labelled RES as an internal standard. The ESI was operated in its negative ion mode while DRG and RES were determined by multiple reaction monitoring (MRM) using precursor-to-product ion transitions of m/z 241.1 → 180.8 and m/z 233.0 → 191.0, respectively. This LC-MS/MS method displayed excellent selectivity, sensitivity (LLOQ = 2.5 ng/ml), accuracy (both intra- and interday mean analytical recovery within 100 ± 15%) and precision (both intra- and interday CV 15%). The mean matrix factors were all within 1.000 ± 0.150 with CV 15%. The pharmacokinetic profiles of DRG were subsequently examined in Sprague-Dawley rats. Upon intravenous administration (4 or 10 mg/kg), DRG displayed very rapid clearance (Cl = 338 ± 66 or 275 ± 30 ml/min/kg) and short mean residence time (MRT = 12.9 ± 4.7 or 10.4 ± 0.5 min). After oral administration of DRG fully solubilized by 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), the plasma profiles of DRG were highly erratic with a low absolute bioavailability (F 9.83 ± 5.31%). When DRG was given at a higher dose (50 mg/kg) in suspension form, the F was increased to 24.1 ± 5.6%. The pharmacokinetic comparison among DRG, RES and some of its hydroxyl analogues stilbenes was performed. The information obtained from this study will facilitate further exploration on DRG as well as other RES derivatives.

This paper based on the basic theory of reliability- centered maintenance (RCM) combined with the characteristics of the high speed train products, analysed and elucidated the time and requirements, premise, the content and the output of the RCM analysis that the high-speed train products carry out; put forward the ideas of organization to implement the RCM analysis, which has a great realistic significance on the RCM analysis.