Quaterization Derivatization with Bis(Pyridine) Iodine Tetrafluoroboride: High-Sensitivity Mass Spectrometric Analysis of Unsaturated Fatty Acids in Human Thyroid Tissues.

Accurate quantification of disease-related unsaturated fatty acids (UFAs) in biomedical samples plays an important role in clinical diagnosis. Here, we reported a quaterization derivatization-stable isotope labeling strategy for accurate quantitative analysis of UFAs by high-performance liquid chromatography-mass spectrometry. [d0]/[d10]-Bis(pyridine) iodine tetrafluoroboride ([d0]/[d10]-IPy2BF4) was employed as the carbon-carbon double bond derivatization reagent with high efficiency and high specificity, to introduce a charge tag on UFAs and avoid the interference of saturated fatty acids. After labeling, the detection sensitivity was significantly enhanced by up to three orders of magnitude compared to intact UFAs. The standard curves showed good linearity (R2 > 0.999) over a wide concentration range. This strategy was successfully applied to determine the content of 12 UFAs in human thyroid carcinoma and para-carcinoma tissues. A significant difference was found in the content of several UFAs between these two kinds of tissues (p < 0.05). These results indicated that the proposed strategy may be valuable for the discovery of abnormal UFA content in early clinical diagnosis.

Chloramine-T-Enabled Mass Spectrometric Analysis of C═C Isomers of Unsaturated Fatty Acids and Phosphatidylcholines in Human Thyroids.

Specific locations of carbon-carbon double bonds (C═C) in lipids often play an essential role in biological processes, and there has been a booming development in C═C composition analysis by mass spectrometry. However, a universal derivatization and fragmentation pattern for the annotation of C═C positions in lipids is still challenging and attractive. To expand this field in lipidomics, a flexible and convenient N-tosylaziridination method was developed, with high derivatization efficiency, sensitivity, and specificity. The derivatization was very fast (15 s), and C═C numbers as well as locations could be pinpointed specifically in tandem mass spectra. By qualitative and quantitative studies of paratumor and tumor thyroid tissues of human beings, the total content of unsaturated fatty acids was suggested to be increased in tumor tissues, and good correlations in and between lysophosphatidylcholines and phosphatidylcholines were revealed by Spearman analysis. Further studies of C═C isomers showed that n-6/n-3 ratios were closely associated with human thyroid tumorigenesis, and high ratios of n-6/n-3 isomers seemed to suffer a high risk of carcinogenesis. Other isomers were not very representative; however, C═C in n-9/n-7 could also be significant for oncology research. Generally, it is supposed that both total amounts and C═C isomer ratios were related to cancer, and N-tosylaziridine derivatization could provide an alternative strategy for the C═C isomer study of disease models.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy.

BACKGROUND: To review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT). METHODS: From April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28-30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. RESULTS: Among the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153). CONCLUSION: Distant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

The outcomes and prognostic factors of patients who underwent reoperation for persistent/recurrent papillary thyroid carcinoma.

BACKGROUND: While the most suitable approach for treating persistent/recurrent papillary thyroid carcinoma (PTC) remains controversial, reoperation may be considered an effective method. The efficacy of reoperation in patients with locoregional persistent/recurrent PTC, especially those with unsatisfactory radioactive iodine (RAI) ablation results, is still uncertain. This study aimed to clarify the clinical management strategies for locoregional persistent/recurrent PTC and to explore factors that may affect long-term patient outcomes after reoperation. METHODS: In total, 124 patients who initially underwent thyroidectomy and variable extents of RAI therapy and finally received reoperation for locoregionally persistent/recurrent PTC were included. The parameters associated with recurrence-free survival (RFS) were analysed using a Cox proportional hazards model. RESULTS: Overall, 124 patients presented with structural disease after initial therapy and underwent secondary surgical resection, of whom 32 patients developed further structural disease during follow-up after reoperation. At the time of reoperation, metastatic lymph nodes with extranodal extension (P = 0.023) and high unstimulated thyroglobulin (unstim-Tg) levels after reoperation (post-reop) (P = 0.001) were independent prognostic factors for RFS. Neither RAI avidity nor the frequency and dose of RAI therapies before reoperation affected RFS. CONCLUSIONS: Reoperation is an ideal clinical treatment strategy for structural locoregional persistent/recurrent PTC, and repeated empirical RAI therapies performed prior to reoperation may not contribute to the long-term outcomes of persistent/recurrent PTC patients. Metastatic lymph nodes with extranodal extension and post-reop unstim-Tg > 10.1 ng/mL may predict a poor prognosis.

Simultaneous Analysis of Fatty Alcohols, Fatty Aldehydes, and Sterols in Thyroid Tissues by Electrospray Ionization-Ion Mobility-Mass Spectrometry Based on Charge Derivatization.

In this work, we developed a rapid and high-sensitivity method for simultaneous analyses of fatty alcohols, fatty aldehydes, and sterols by combining the optimized derivatization reaction with electrospray ionization-ion mobility-mass spectrometry (ESI-IM-MS). Pyridine and thionyl chloride were used as derivatization reagents as they were easily removed after the derivatization reaction and could generate permanently charged tags on different functional groups including hydroxyls and aldehydes. Through this one-step derivatization reaction, the sensitivity of detection for fatty alcohols, fatty aldehydes, and sterols was significantly increased. Moreover, the introduction of ion mobility spectrometry (IMS), offering an additional resolution power, ensured more sensitive and accurate detection of derivative products without increasing analytical time. Being connected with high-performance liquid chromatography, more than 15 kinds of compounds were analyzed within 4 min. Relative quantification using peak intensity ratios between d0-/d5-labeled ions were subsequently applied for analyzing these 15 kinds of compounds in human thyroid carcinoma and para-carcinoma tissues. The results showed significant differences in content of some analytes between these two kinds of tissues (p < 0.05). The correlations between most of the analytes in thyroid carcinoma tissues are better than the correlations in para-carcinoma tissues.

Tripartite motif containing 14: An oncogene in papillary thyroid carcinoma.

Tripartite motif (TRIM)-containing protein 14 (TRIM14) is implicated in many malignancies. Presently, we studied whether TRIM14 played a role in human papillary thyroid carcinoma (PTC). Herein, TRIM14 was up-regulated in tumor tissues when compared with normal thyroid samples. Among PTC patients, enhanced TRIM14 predicted short recurrence free survival (RFS) time. Then, we found that knockdown of TRIM14 in human PTC K1 cells inhibited cell proliferation, induced cell apoptosis and prevented the tumorigenicity in nude mice. On the contrary, TRIM14 overexpression in human PTC TPC1 cells promoted cell proliferation while inhibited cell apoptosis. TRIM14 exerted its oncogenic activities via promoting the activation of signal transducer and activator of transcription 3 (STAT3). Further, TRIM14 interacted with the suppressor of cytokine-signaling-1 (SOCS1), a negative regulator of STAT3 activation, and knockdown of TRIM14 inhibited SOCS1 ubiquitination. In conclusion, TRIM14 may be a prognostic factor and oncogene in PTC, and may be a potential target for PTC intervention.

High Ratio of Early Postoperative Calcitonin to Preoperative Calcitonin Could be a Novel Indicator of Poor Prognosis in Patients with Biochemical Incomplete Responses in Sporadic Medullary Thyroid Cancer.

OBJECTIVE: In a cohort of medullary thyroid cancer (MTC) patients with biochemical incomplete responses, 37 to 48% developed structural persistent disease; however, few indictors were available to distinguish those patients who were more likely to develop structural disease. We hypothesized that the relationship between preoperative calcitonin (Ctn) and postoperative Ctn (within 3 days after surgery) could be used to predict early prognosis of these patients. METHODS: A total of 92 sporadic MTC patients were enrolled in this study. Our team proposed a novel indicator of structural persistent MTC called the calcitonin ratio (CR; CR = postoperative Ctn/preoperative Ctn). Cox regression models and the Kaplan-Meier method were used to evaluate the prognostic capability of CR. The area under the time-dependent receiver-operating characteristic curves (AUC) and the Harrell concordance index (C-index) were used for analysis. RESULTS: The cutoff CR value used to determine MTC prognosis was 0.15. Multivariate Cox analysis revealed that CR (hazard ratio [HR]: 22.974, 95% confidence interval [CI]: 3.259 to 161.959, P = .002), tumor-node-metastasis (HR: 3.968, 95% CI: 1.360 to 21.857; P = .031), and multifocality (HR: 8.466, 95% CI: 1.286 to 55.716; P = .026) independently correlated with MTC prognosis. Kaplan-Meier survival curves demonstrated a lower proportion with structural persistent disease in patients with CR <0.15 (P<.001). The 3, 5, and 10-year AUC values were 0.798, 0.752, and 0.743, respectively. The C-index of CR was 0.788 (95% CI: 0.763 to 0.813). CONCLUSION: In this study, CR was identified as a sensitive and specific risk stratification marker for patients with biochemical incomplete responses in sporadic MTC. ABBREVIATIONS: ATA = American Thyroid Association; AUC = area under curve; CEA = carcinoembryonic antigen; CR = calcitonin ratio; Ctn = calcitonin; HR = hazard ratio; MTC = medullary thyroid cancer; ROC = receiver operating characteristic; TNM = tumor-node-metastasis.

LHPP inhibits cell growth and migration and triggers autophagy in papillary thyroid cancer by regulating the AKT/AMPK/mTOR signaling pathway.

In recent decades, the incidence rate of papillary thyroid carcinoma (PTC) has been rapidly increasing. However, the molecular mechanism of the physiological and pathological processes of PTC is still largely unknown. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a tumor suppressor and exerts anti-tumor effect in several human cancers, while the role and underlying mechanism of LHPP in PTC remain vague. In this study, we firstly evaluated the roles of LHPP in PTC and explored its underlying mechanism. Using clinical tissue samples, we detected the level of LHPP in PTC tissues and in matched adjacent normal tissues. Lower level of LHPP was found in PTC tissues than in matched adjacent normal tissues. Similar LHPP expression pattern was found in PTC cell lines when compared with that in normal human thyroid follicular epithelial cells. Then, we over-expressed LHPP in three PTC cell lines and results showed that ectopic LHPP expression consistently reduced cell viability, proliferation, and migration and triggered cell autophagy. Furthermore, over-expression of LHPP inhibited the activation of the AKT/mTOR pathway and promoted the AMPK signaling pathway. In addition, the activation of AKT/mTOR and inhibition of AMPK signaling pathways restored the role of ectopic LHPP expression in PTC cell lines, indicating that LHPP exerts its anti-tumor activity through regulating the AKT/AMPK/mTOR pathway. Ultimately, we illustrated that ectopic LHPP expression inhibited PTC tumor growth in vivo. In conclusion, we revealed that LHPP has an anti-tumor effect in PTC and indicated that LHPP might serve as an effective diagnostic and therapeutic target for PTC.

Derivatization Strategy for Simultaneous Molecular Imaging of Phospholipids and Low-Abundance Free Fatty Acids in Thyroid Cancer Tissue Sections.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has been applied in many fields for detecting and imaging a variety of metabolites. In cancer research, this fast-growing imaging method also helps to elucidate the connection between the changes of metabolites in the microenvironment and the proliferation and survival of cancer cells. Free fatty acids (FFAs) are a vital building block of phospholipids (PLs) that can serve as a second cellular messenger and provide nutrients in the cancer microenvironment. The metabolism process of FFAs and PLs is highly relevant to the initiation and progression of different cancers. To better understand the metabolism process in cancer tissues, simultaneously detecting and imaging FFAs and PLs is essential. Despite the crucial developments that have been performed in the field of lipids imaging, FFAs and PLs have rarely been detected and imaged simultaneously in positive ion mode with good detection sensitivity. In this work, an on-tissue derivatization method was used to add a permanently quaternary amine onto FFAs; then, the FFAs and PLs were simultaneously imaged in positive ion mode. The derivatized FFAs are suitable for detection in positive ion mode. In comparison with the traditional matrix and the previous derivatization method, our derivatization reagent has a higher sensitivity for imaging FFAs. In addition, for simultaneous imaging analysis of FFAs and PLs, the number of imaged FFAs and PLs is greater than that with the previous on-tissue derivatization method. This high-sensitivity on-tissue derivatization method was applied to detect and image PLs and fatty acids in thyroid cancer tissues. In the MSI experiment, FFA derivatives and PLs were imaged while molecular localization and tissue integrity were maintained. Meanwhile, the correlation between PLs and FFAs was also studied, and the results showed that the correlations between saturated FFAs of C16:0 and C18:0 and PLs are better than the correlations of unsaturated FFAs with PLs.

A Novel N Staging System for Predicting Survival in Patients with Medullary Thyroid Cancer.

INTRODUCTION: Despite the crucially prognostic value of lymph node metastasis (LNM) in patients with medullary thyroid cancer (MTC), only the LNM compartment alone was reflected in the 8th edition of the American Joint Committee on Cancer (AJCC) system. OBJECTIVE: This study aimed to incorporate the metastatic lymph node number and metastatic lymph node ratio to generate a more accurate and appropriate N staging system for patients with MTC based on recursive partitioning analysis. DESIGN, SETTING, AND PATIENTS: Two cohorts were included in the analysis, including 1374 MTC patients from the Surveillance, Epidemiology, and End Results database as the derivation cohort, and 164 patients from Fudan University Shanghai Cancer Center as the validation cohort. The predictive performance of the alternative proposed N staging system was compared with that of the 8th AJCC system by using the Harrell concordance index (C-index) and the area under the receiver operating characteristic curve (AUC). RESULTS: In the derivation cohort, the C-index and the AUC at 10 years were 0.778 and 0.789, respectively, for the novel N staging system, and 0.749 and 0.741, respectively, for the 8th AJCC N staging system. Similar trends were also observed in the validation cohort. The proposed N staging system had a better prognostic performance. CONCLUSION: With some improvements, the novel N staging system for MTC suggested from this research may be assessed for potential adoption in the next edition of the AJCC N staging system.

Outcome of radical resection and postoperative radiotherapy for thyroid carcinoma showing thymus-like differentiation.

BACKGROUND: Carcinoma showing thymus-like differentiation (CASTLE) is a rare disease that is difficult to diagnose. The aim of this study was to assess the effects of combined-modality treatment in CASTLE patients. METHODS: We retrospectively studied patients identified between January 1, 2000 and December 31, 2009 as having CASTLE and who subsequently underwent surgery and radiotherapy or chemotherapy. Preoperative laboratory findings, ultrasonographic (US) and computed tomographic (CT) features, and fine-needle aspiration biopsy (FNAB) specimens were evaluated. RESULTS: Seven patients with CASTLE were identified (four men, three women). The median age at initial diagnosis was 48 years (range 25-56 years). The five newly diagnosed patients were treated with curative surgery and postoperative radiotherapy, whereas two patients with recurrent disease were treated with salvage surgery plus radiotherapy or chemotherapy. All patients were disease-free at a median follow-up period of 34 months (range 12-61 months). The pattern of immunohistochemical staining was similar to that of thymic carcinoma. Specimens from all seven patients stained positively for CD5, CD117, and cytokeratin but were uniformly negative for thyroglobulin, thyroid transcription factor 1 (TTF-1), and calcitonin. CONCLUSIONS: Patients with CASTLE have excellent outcomes after curative resection and postoperative radiotherapy compared with patients with anaplastic thyroid carcinoma. Even patients with local recurrent disease benefited from salvage surgery with subsequent operation and/or radiotherapy. CD5 immunohistochemical staining on FNAB samples may help identify the possible entities that are part of the differential diagnosis.

LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p.

While long noncoding RNAs (lncRNAs) have been reported to play an important role in human cancer types, they remain poorly understood in papillary thyroid carcinoma (PTC). The aim of this study was to use genome-wide expression profiling to identify lncRNAs acting as competing endogenous RNAs (ceRNAs) in PTC. We constructed a ceRNA network based on our lncRNA microarray data and validated the correlation between myocardial infarction-associated transcript lncRNA (MIAT), miRNA-150-5p, and EZH2 in vitro and in vivo. We found 15 lncRNAs, 28 miRNAs, and hundreds of mRNAs involved in this ceRNA network. Splendid positive correlations were found between the MIAT and EZH2 expression in types of cancer in TCGA data. Besides, significant differences in MIAT/EZH2 expression were found among various clinicopathological features. Gain- and loss-of-function experiments revealed that MIAT inhibited cell proliferation and migration in vitro. Moreover, EZH2 was identified as a direct downstream target of miR-150-5p in PTC cells. Restoration of EZH2 expression partially abolished the biological effects of miR-150-5p. Furthermore, overexpression of MIAT was inversely correlated with miR-150-5p expression. Knockdown of MIAT produced significant behavioral alter maybe partly due to the function of the MIAT-150-5p-EZH2 network. Our findings suggest MIAT may inhibit EZH2 expression and promote PTC cell invasion via the miR-150/EZH2 pathway. Therefore, MIAT may serve as a valuable prognostic biomarker and therapeutic target for PTC.

Clinical and Molecular Characterizations of Papillary Thyroid Cancer in Children and Young Adults: A Multicenter Retrospective Study.

Background: Papillary thyroid carcinoma (PTC) is a rare malignancy in children and young adults (CAYA). It often presents with aggressive disease patterns and advanced stages, which are clinically distinct from those in adult patients. In this study, we sought to characterize and better understand the clinical variants of PTC in CAYA and explore the underlying mechanisms. Methods: CAYA patients (age ≤18 years) diagnosed with PTC between June 2006 and June 2018 were retrospectively recruited from five hospitals. Demographic information, pathological data, and follow-up status were recorded. Tumor samples obtained from 20 children (mean age 15.15 years) and 10 adults (mean age 38.80 years) underwent comprehensive whole transcriptome sequencing. Differentially expressed genes (DEGs), mutational landscape, and immune infiltration were analyzed. Results: A total of 217 CAYA-PTC patients (162 females and 55 males) with an average age of 14.38 ± 3.53 years (range 2-18) were included. Lymph node metastasis (LNM) was observed in 85.71%, of which 57.60% were in the lateral cervical compartment. Disease recurred in 28 of 217 (12.90%) patients with a median follow-up of 4.76 years. Multivariate logistic regression analysis revealed that age, bilateral disease, extrathyroidal extension, and coexisting Hashimoto's thyroiditis (co-HT) were independent risk factors for LNM, while co-HT was the only risk factor for recurrence. Using whole transcriptome sequencing of PTC tissues, we identified 301 DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that differences in immune mediators played important roles, based on the distributions of mutation frequencies, types, and expression levels between CAYA and adult patients. Based on the integrated data sets, we identified significantly mutated immune genes, cluster of differentiation 24 (CD24), coagulation factor 12 (F12), coagulation factor 5 (F5), integrin subunit alpha 3 (ITGA3), and retinoic acid early transcript 1L (RAET1L), which were then verified by immunohistochemistry. Furthermore, resting mast cells, resting natural killer cells, plasma cells, and regulatory T cells were different in the CAYA-PTC group and correlated with the expression of immune checkpoints. Conclusions: There are considerable variabilities that may contribute to the different clinical presentations between CAYA and adult PTC patients, among which the decrease in protective immune cells may be a factor. Collectively, our results add to the possible biological mechanisms involved in CAYA-PTC.

Identification of differentially expressed genes and signaling pathways in papillary thyroid cancer: a study based on integrated microarray and bioinformatics analysis.

BACKGROUND: The techniques of DNA microarray and bioinformatic analysis have exhibited efficiency in identifying dysregulated gene expression in human cancers. In this study, we used integrated bioinformatics analysis to improve our understanding of the pathogenesis of papillary thyroid cancer (PTC). METHODS: In this study, we integrated four Gene Expression Omnibus (GEO) datasets, GSE33630, GSE35570, GSE60542 and GSE29265, including 136 normal samples and 157 PTC specimens. The contents of the four datasets are based on GPL570, an Affymetrix Human Genome U133 Plus 2.0 array. Gene ontology (GO) analysis was used to identify characteristic the biological attributes of differentially expressed genes (DEGs) between PTC and normal samples. GO annotation was performed on the DEGs obtained, and the process relied on the DAVID online tool. Kyoto Encyclopedia of Genes and Genomes (KEGG) approach enrichment analyses were adopted to obtain the basic functions of the DEGs. The KOBAS online analysis database was used to complete DEG KEGG pathway comparison and analysis. The search tool (STRING) database was mainly used to search for interacting genes and complete the construction of protein-protein interaction (PPI) networks. RESULTS: Five hundred-ninety DEGs were consistently expressed in the four datasets; 327 of them were upregulated, while 263 were downregulated. Ten DEGs, including five upregulated (ENTPD1, THRSP, KLK10, ADAMTS9, MIR31HG) and five downregulated (SCARA5, EPHB1, CHRDL1, LOC440934, FOXP2) genes, were randomly selected for q-PCR in our own tissue samples to validate the integrated data. The most highly enriched GO terms were extracellular exosome (GO:0070062), cell adhesion (GO:0070062), positive regulation of gene expression (GO:0010628), and extracellular matrix (ECM) organization (GO:0030198). KEGG pathway analysis was performed, and it was found that abnormally expressed genes effectively participated in pathways such as tyrosine metabolism, complement and coagulation cascades, cell adhesion molecules (CAMs), transcriptional misregulation and ECM-receptor interaction pathways. CONCLUSIONS: Five hundred-ninety DEGs were identified in PTC by integrated microarray analysis. The GO and KEGG analyses presented here suggest that the DEGs were enriched in extracellular exosome, tyrosine metabolism, CAMs, complement and coagulation cascades, transcriptional misregulation and ECM-receptor interaction pathways. Functional studies of PTC should focus on these pathways.

Characteristics and prognosis of primary thyroid non-Hodgkin's lymphoma in Chinese patients.

BACKGROUND AND OBJECTIVES: There exists no universally accepted treatment for primary thyroid non-Hodgkin's lymphoma (TNHL) due to the rarity of this entity. The aim of this study is to assess the role of surgery and to explore prognostic factors in Chinese TNHL patients. METHODS: Patient presentations, pathologies, surgical interventions, multidisciplinary treatment, prognostic factors and the value of fine needle aspiration were analyzed. RESULTS: Between 1991 and 2007, 40 patients of TNHL were diagnosed. Thirty-eight patients underwent an initial surgical procedure. Further treatments consisted of radiotherapy or chemotherapy alone, and the majority of patients were treated with combined chemo-radiation. After a median follow-up of 95 months, the 5-year overall survival (OS) and relapse-free survival (RFS) was 82% and 74%, respectively. Survival curves showed no significant difference between therapeutic operations when compared with diagnostic operations. A univariate analysis showed both International Prognostic Index (IPI) and staging significantly influenced OS and RFS. In multivariate analysis, IPI was found to be the only prognostic factor. CONCLUSIONS: Combined chemotherapy and radiotherapy may offer better outcome without the need for extensive resection, and surgery should be reserved to providing tissue for diagnosis. The patients with low-intermediate risk (IPI = 2) or stage IIE need be treated more aggressively.

A Comparison of Two Operation Methods Revealed the Risk Factors and the Necessity of LN-prRLN Dissection in Papillary Thyroid Carcinoma: A Retrospective Cohort Study in FUSCC.

BACKGROUND: Although the American Thyroid Association (ATA) guidelines indicate that central lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) should be routinely dissected, pr-RLN dissection is often neglected due to the high risk of injury to the recurrent laryngeal nerve (RLN). The purpose of this study was to investigate the risk factors associated with LN-prRLN metastasis in patients with papillary thyroid carcinoma (PTC) by preoperative examination and the indications for LN-prRLN dissection. METHODS: A total of 1487 consecutive patients with PTC who underwent total thyroidectomy or right lobectomy plus isthmic resection with central LN dissection (CLND) were divided into two groups: patients with LN-prRLN dissection (group A) and patients without LN-prRLN dissection (group B). Clinicopathologic data were reviewed of the patients who were operated on by the same thyroid surgery team in the Department of Head Neck Surgery, Fudan University Shanghai Cancer Center (FUSCC) between August 2011 and May 2019. The relationships of LN-prRLN metastasis with clinicopathologic characteristics were analyzed by univariate and multivariate logistic regression. RESULTS: The incidence of LN-prRLN metastasis was 34.1% (129/378). Univariate analysis showed that sex (P ≤ 0.001), tumor size (P ≤ 0.001), extrathyroidal extension (P=0.002), concurrent Hashimoto's thyroiditis (P=0.009), cLNMa (central lymph nodes anterior to the right recurrent laryngeal nerve) (P ≤ 0.001), cLNMa number (P ≤ 0.001), and lateral LN metastasis (LLNM) (P ≤ 0.001) were significantly associated with LN-prRLN metastasis in PTC. Multivariate logistic regression analysis revealed that tumor size (P=0.039), cLNMa (P=0.001), and LLNM (P=0.025) were independent risk factors for LN-prRLN metastasis in patients with PTC. Although there was no significant difference between the two groups in recurrence, we found that 4 cases relapsed in the LN-prRLN compartment in group B, while none relapsed in group A. CONCLUSION: LN-prRLN metastasis is often identified in patients with PTC. Patients with large tumor sizes, cLNMa and LLNM are at a high risk of LN-prRLN metastasis and should be recommended for careful LN-prRLN dissection.

The limited role of elective neck dissection in patients with cN0 salivary gland carcinoma.

PURPOSE: To evaluate whether elective neck dissection (END) was beneficial for cN0 patients with salivary gland carcinoma. MATERIALS AND METHODS: The rates of regional failure-free survival and disease-free survival were calculated using Kaplan-Meier methods and Cox models. The risk factors for occult lymph node metastasis (OLNM) in cN0 patients undergoing END was analyzed using logistic regression. A nomogram was formulated to calculate the estimated probability of OLNM. RESULTS: Neck dissection was performed in 84 patients (43.3%). OLNM was detected in eight of the patients who underwent END. During the follow-up period, regional recurrences involving cervical lymph nodes were found in 10 patients. Cox model analysis revealed that neck dissection was not related to regional failure-free survival and disease-free survival. Logistic regression analysis revealed that older age, neural symptoms, and positive adjacent lymph nodes were associated with OLNM. A nomogram comprising age, neural symptoms, and adjacent lymph nodes was developed to predict the risk of OLNM. CONCLUSION: The incidence of OLNM was low in cN0 patients after detailed preoperative evaluations. There was no strong evidence supporting END as a conventional therapy in cN0 patients with salivary cancers. Our nomogram is a simple and practical instrument for strengthening the prediction of OLNM.

Long noncoding RNA RP11-547D24.1 regulates proliferation and migration in papillary thyroid carcinoma: Identification and validation of a novel long noncoding RNA through integrated analysis of TCGA database.

Long noncoding RNAs (lncRNAs) are known to be key regulators of numerous biological processes, and substantial evidence supports that abnormal lncRNA expression plays a significant role in tumorigenesis and tumor progression. However, the mechanism by which lncRNAs function in thyroid carcinoma are still unclear. To investigate the role of lncRNAs in the tumorigenesis of papillary thyroid carcinoma (PTC), we analyzed lncRNA data in The Cancer Genome Atlas RNA-Seq database. A comparison of lncRNAs in cancerous thyroid tissues and normal tissues revealed hundreds of differentially expressed lncRNAs. Of 7589 lncRNAs identified in 561 thyroid cancer cases (503 cancerous tissues and 58 normal tissues), the expression levels of 144 were found to be aberrant (|log2 fold change| >2 and adjusted P < 0.05). The top 10 lncRNAs with the most significant differences were LINC01977, RP11-363E7.4, RP3-483K16.4, RP11-547D24.1, RUNDC3A-AS1, AC093609.1, CTD-2008L17.2, HAGLROS, UNC5B-AS1, and LINC01354. In addition, CTD-2008L17.2, HAGLROS, AC093609.1, UNC5B-AS1, and RUNDC3A-AS1 were shown to play vital roles in determining the histological cancer type. Furthermore, RP11-547D24.1 and UNC5B-AS1 could distinguish patients with different stages of PTC. The lncRNA RP11-547D24.1 was validated by loss-of-function assays, revealing that downregulation of this lncRNA regulates thyroid tumor cell proliferation and apoptosis, invasion, and migration. This study demonstrates the potential for using lncRNAs to interpret the pathogenesis and development of PTC.

The number and ratio of positive lymph nodes are independent prognostic factors for patients with major salivary gland cancer: Results from the surveillance, epidemiology, and End Results dataset.

INTRODUCTION: To investigate whether the positive lymph node number (PLNN) and positive lymph node ratio (PLNR) could predict the prognosis of patients with major salivary gland cancer (MSGC) and to identify the optimal cutoff points for these variables that stratify patients according to their risk of survival. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify all patients with MSGC between 1988 and 2014. A logistic regression analysis was carried out to evaluate the risk factors for lymph node metastasis (LNM) in MSGC. The X-tile program was used to identify the cutoff values for the PLNN and PLNR in MSGC patients with LNM. Cox proportional hazards regression models were performed to identify the predictors of cancer-specific survival (CSS). RESULTS: In the SEER database, 8668 eligible patients were identified and 3046 of them had LNM. The logistic regression analysis indicated that older age, male sex, larger tumor size, higher grade, tumor extension and high-risk pathology were associated with LNM. The X-tile program showed that a PLNN>4 and a PLNR>0.15 were prognostic indicators of CSS. A multivariable analysis indicated that, after the factors that might potentially affect the prognosis were adjusted for, the PLNN and PLNR were still associated with CSS. CONCLUSIONS: Our Results demonstrated that the PLNN and PLNR were independent prognostic indicators for MSGC patients with lymph node metastasis.