PLS3 promotes papillary thyroid carcinoma progression by activating the Notch signaling pathway.

Thyroid cancer is the most common endocrine malignancy worldwide. Although significant progress has been made in understanding the genetic and molecular alterations that drive thyroid cancer, the mechanisms underlying thyroid tumor progression remain unclear. In this study, we explored the involvement of Plastin-3 (PLS3) in the progression of papillary thyroid cancer and elucidated the underlying molecular mechanisms. We first analyzed clinical samples from papillary thyroid cancer patients and found that PLS3 expression was significantly upregulated in tumor tissues compared to adjacent normal tissues. Moreover, high PLS3 expression was associated with advanced tumor stage and poor prognosis. Further in vitro and in vivo experiments showed that PLS3 could promote the proliferation, migration, and invasive behavior of papillary thyroid cancer cells, while PLS3 knockdown suppressed these processes. Mechanistically, we found that PLS3 promoted papillary thyroid cancer progression by activating the Notch signaling pathway. Specifically, PLS3 upregulated the expression of Notch receptors (Notch1) and downstream target gene (Hes1) in papillary thyroid cancer cells. In summary, our findings collectively indicate that PLS3 plays a pivotal role in driving the progression of papillary thyroid cancer and holds promise as a viable therapeutic target for the treatment of this disease.

Integrated analysis of tumor microenvironment features to establish a diagnostic model for papillary thyroid cancer using bulk and single-cell RNA sequencing technology.

BACKGROUND: Characterizing tumor microenvironment using single-cell RNA sequencing has been a promising strategy for cancer diagnosis and treatment. However, a few studies have focused on diagnosing papillary thyroid cancer (PTC) through this technology. Therefore, our study explored tumor microenvironment (TME) features and identified potential biomarkers to establish a diagnostic model for papillary thyroid cancer. METHODS: The cell types were identified using the markers from the CellMarker database and published research. The CellChat package was conducted to analyze the cell-cell interaction. The SCEVAN package was used to identify malignant thyroid cells. The SCP package was used to perform multiple single-cell downstream analyses, such as GSEA analysis, enrichment analysis, pseudotime trajectory analysis, and differential expression analysis. The diagnostic model of PTC was estimated using the calibration curves, receiver operating characteristic curves, and decision curve analysis. RT-qPCR was performed to validate the expression of candidate genes in human papillary thyroid samples. RESULTS: Eight cell types were identified in the scRNA-seq dataset by published cell markers. Extensive cell-cell interactions like FN1/ITGB1 existed in PTC tissues. We identified 26 critical genes related to PTC progression. Further, eight subgroups of PTC tumor cells were identified and exhibited high heterogeneity. The MDK/LRP1, MDK/ALK, GAS6/MERTK, and GAS6/AXL were identified as potential ligand-receptor pairs involved in the interactions between fibroblasts/endothelial cells and tumor cells. Eventually, the diagnostic model constructed by TRPC5, TENM1, NELL2, DMD, SLC35F3, and AUTS2 showed a good efficiency for distinguishing the PTC and normal tissues. CONCLUSIONS: Our study comprehensively characterized the tumor microenvironment in papillary thyroid cancer. Through combined analysis with bulk RNA-seq, six potential diagnostic biomarkers were identified and validated. The diagnostic model we constructed was a promising tool for PTC diagnosis. Our findings provide new insights into the heterogeneity of thyroid cancer and the theoretical basis for diagnosing thyroid cancer.

Extrathyroidal extension or tumor size of primary lesion influences thyroid cancer outcomes.

AIMS: Extrathyroidal extension (ETE) is a determined factor of T3 and T4 stage of differentiated thyroid cancer (DTC) in American Joint Committee on Cancer. We aimed to compare clinical outcomes between different extent of ETE according to tumor size. METHODS: Patients diagnosed with DTC were collected from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. They were categorized into two groups by presence of lymph node metastases (LNM) or distant metastases (DM): group A: no presence of LNM and DM, and group B: presence of LNM or DM. Each group was further divided into four groups according to tumor size: <1 cm, 1-2 cm, 2-4 cm, >4 cm. ETE was divided into three groups by the extent: no ETE, microscopic ETE, and macroscopic ETE. Kaplan-Meier method and log-rank test were used to analyze cancer-specific survival (CSS). RESULTS: 91,975 patients were included. In groups A and B, for tumor size 1 cm, there was no significant difference in CSS between no ETE and microscopic ETE, while a significant difference was observed between no ETE and macroscopic ETE. For tumor size >1 cm, there were significant differences in CSS (both no ETE vs. micro ETE and no ETE vs. macro ETE). CONCLUSION: We suggests that when tumor size is more than 1 cm, micro ETE is significantly associated with poorer outcome. T3 and T4 stages may take account into tumor size rather than merely based on the presence and extent of ETE. It may be prudent to revisit the omission of micro ETE in TNM staging.

CTHRC1 promotes anaplastic thyroid cancer progression by upregulating the proliferation, migration, and invasion of tumor cells.

Anaplastic thyroid carcinoma (ATC) is an extremely aggressive tumor with a high mortality rate and poor prognosis. However, the pathogenesis of ATC is complex and poorly understood, and the effective treatment options are limited. Analysis of data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases showed that collagen triple helix repeat containing-1 (CTHRC1) was specifically upregulated in ATC tissues and was negatively correlated with overall survival (OS) in thyroid carcinoma patients. In vitro knockdown of CTHRC1 dramatically decreased the proliferation, migration, and invasion abilities of ATC cells, and in vivo studies in BALB/c nude mice confirmed that CTHRC1 knockdown significantly inhibited tumor growth. Mechanistically, CTHRC1 knockdown was found to suppress the Wnt/ß-catenin pathway and epithelial-mesenchymal transition (EMT) at the protein level. These findings suggest that CTHRC1 promotes the progression of ATC via upregulating tumor cell proliferation, migration, and invasion, which may be achieved by activating the Wnt/ß-catenin pathway and EMT.

AXL, along with PROS1, is overexpressed in papillary thyroid carcinoma and regulates its biological behaviour.

BACKGROUND: AXL, a TAM tyrosine kinase receptor, plays an essential role in the pathogenesis of various solid tumours. This study explores the role of AXL and its ligand PROS1 in the generation and biological behaviour of papillary thyroid cancer (PTC). METHODS: The expression levels of AXL in PTC cancer tissue were analysed using immunohistochemistry (IHC) staining. The expression levels of AXL in PTC and normal thyroid cell lines were analysed using real-time quantitative polymerase chain reaction (RT-qPCR). CCK-8 was used to assess the proliferation of the PTC cell line with and without the effect of the AXL inhibitor (R428). Scratching assays played a role in evaluating the cell migration rate. RESULTS: PROS1 and AXL were expressed in TPC-1, B-CPAP, and Nthy-Ori 3-1 cells at different levels. Expression was significantly higher in PTC cell lines (TPC-1 and B-CPAP) than in the normal thyroid cell line (Nthy-Ori 3-1) (p < 0.05). In addition, AXL expression in PTC tissues was significantly higher than in adjacent normal tissues (p < 0.05). CCK-8 experiments confirmed that R428 suppresses the proliferation of PTC cell lines in a dose-dependent manner, with an increase in concentration from 0.5 to 4 µM, decreasing the inhibitory effect (p < 0.01). In addition, R428 inhibited PTC cell line migration to different degrees in a range of concentrations from 0.5 to 2 µM compared to control cells (p < 0.01). CONCLUSION: PROS1 and its downstream receptor AXL expression were significantly higher in PTC than in normal thyroid cells. AXL expression was also higher in human PTC tissues than in normal thyroid tissues. Inhibiting the PROS1-AXL-mediated TAM signaling pathway via the AXL blocker R428 suppressed the proliferation and migration of human PTC cells, highlighting the role of this cascade in human PTC development and progression.

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model.

Background: Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat. Methods: Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed. Results: Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators. Conclusion: Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.

Analysis of Clinicopathological Characteristics and Prognosis of Carcinosarcoma of the Breast.

Background: Few cases of carcinosarcoma of the breast have been reported because of its low incidence rate and rapid progression. Seeking effective therapeutic methods becomes urgent in clinical practice. This study was aimed to investigate the clinical characteristics of carcinosarcoma of the breast and to explore proper therapeutic methods for patients with this rare tumor. Methods: We conducted a retrospective analysis on 47 patients with carcinosarcoma of the breast receiving treatment in our hospital from 2003 to 2020. Most of these patients received primary surgery followed by adjuvant chemotherapy, while four patients had lumpectomy only. Statistics showed no preference in age and menopausal status of patients. Results: The overall survival rate and progression-free survival rate of all patients at a median follow-up time of 33 months were 63.8% and 57.4%, respectively. Tumor size at diagnosis and chemotherapy strategies were both significant prognostic factors in reference to disease-free survival (DFS) and overall survival (OS) of the patients (tumor size: p=0.023 for DFS and p=0.021 for OS; therapeutic method: p=0.041 for DFS and p=0.024 for OS). N stage at diagnosis was significant only with reference to overall survival of the patients (p=0.009). EGFR expression was positive in some patients. Conclusions: Our results elucidated that the patients received comprehensive therapy, especially adjuvant chemotherapy was indispensable for better outcomes. Early detection and treatment were necessary for a higher survival rate when the tumor size was less than 5 cm without lymph node metastasis. Prospective outcomes with novel strategies targeting EGFR need to be further investigated.

Prospective, randomized, controlled, noninferiority clinical trial to evaluate the safety and efficacy of absorbable macroporous polysaccharide composites as adjunct to hemostasis during open surgery.

BACKGROUND: To address intraoperative bleeding in cardiac surgery, reducing blood transfusion requirements, is mandatory to achieve effective hemostasis. Hemostatic agents may limit localized persistent bleeding. The introduction of carboxymethyl-chitosan component into the hemostatic agent and the application of the radiation crosslinking technique maintain its capacity for achieving intraoperative hemostasis, thus increasing the clinical utility. METHODS: A prospective, noninferiority and randomized controlled clinical trial to compare the safety and efficacy of absorbable macroporous polysaccharide composites (AMPC, treatment group) with compound microporous polysaccharide hemostatic powder (CMPHP, control group) (2:1 ratio) as adjuncts to hemostasis in open surgery. The main indication was used for hemostasis in various traumatic hemorrhage areas, including cardiothoracic, vascular, and general surgery. The primary endpoint was success rate of hemostasis within 300 s (at a 10% noninferiority margin). The secondary endpoint was hemostasis time. Both endpoints were assessed in the modified intention-to-treat (MITT) population. Safety parameters were assessed. This study is fully compliant with the CONSORT statement. RESULTS: Randomized patients in AMPC and CMPHP groups were 168 and 84, respectively. In MITT population, the success rates of hemostasis within 300 s were 98.8% (163 of 165) in AMPC and 94.0% (78 of 83) in CMPHP (treatment difference 4.8% [95% CI -0.57% to 10.20%]). AMPC was thus noninferior to CMPHP. Hemostasis time (median [interquartile range]) with AMPC (87 [52.5, 180] s) was better than CMPHP (110 [54.5, 181] s). Changes in laboratory parameters over time and shifts to abnormal values were typical of surgeries and similar between two groups. No noticeable adverse effects associated with AMPC or CMPHP were observed. CONCLUSIONS: AMPC is well tolerated as topical hemostatic agent, noninferior to commercial CMPHP, and exhibits excellent safety. This study provides a novel hemostatic agent which appears to offer significant clinical advantage in various hemorrhage areas.

Cathepsin F genetic mutation is associated with familial papillary thyroid cancer.

BACKGROUND: Thyroid cancer is one of the most common cancers in the world. Genetic factors are important in the occurrence and development of thyroid cancer, and genetic diagnosis has become an important basis for the prognosis of benign and malignant nodules. We identify a family of six siblings with inherited thyroid cancer susceptibility. All six members of this generation have been definitely diagnosed with papillary thyroid carcinoma. This work aims at confirming the relevant causative genes for thyroid cancer in this pedigree. METHODS: We extract DNA from the peripheral blood of six individuals and perform whole genome sequencing. Sanger sequencing and immunohistochemistry further testify the cathepsin F (CTSF) mutation and expression. RESULTS: We identify 57 single nucleotide variations (SNVs) out of at least 4 affected family members via certain filter criteria. The CTSF gene found in five of the six family members is here considered the most promising candidate gene mutation for familial thyroid cancer. Besides, our research also proves several known genes including CTSB, TEKT4, ESR1, MSH6, DIRC3, GNAS, and BANCR that act as probable oncogenic drivers in this family. The Sanger sequencing identifies the existence and veracity of CTSF somatic mutations. The CTSF immunohistochemistry of thyroid cancer tissue specimens displays that higher CTSF expression in mutated patients than that in wild-type patient as well as pericarcinomatous tissue. CONCLUSIONS: We conclude that the evaluation of CTSF gene mutations of patients in thyroid cancer families may be predictive and valuable for the familial heredity of thyroid cancer.

Single-Cell RNA Sequencing Revealed a 3-Gene Panel Predicted the Diagnosis and Prognosis of Thyroid Papillary Carcinoma and Associated With Tumor Immune Microenvironment.

Objective: The objective of this research was to screen prognostic related genes of thyroid papillary carcinoma (PTC) by single-cell RNA sequencing (scRNA-seq), to construct the diagnostic and prognostic models based on The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) data, and to evaluate the association between tumor immune microenvironment and the prognostic model. Method: The differentially expressed genes (DEGs) and tumor evolution were analyzed by scRNA-seq based on public databases. The potential regulatory networks of DEGs related to prognosis were analyzed by multi-omics data in the THCA. Logistic regression and Cox proportional hazards regression were utilized to construct the diagnosis and prognostic model of PTC. The performance of the diagnostic model was verified by bulk RNA sequencing (RNA-seq) of our cohort. The tumor immune microenvironment associated with the prognostic model was evaluated using multi-omics data. In addition, qRT-PCR was performed on tumor tissues and adjacent normal tissues of 20 patients to verify the expression levels of DEGs. Results: The DEGs screened by scRNA-seq can distinguish between tumor and healthy samples. DEGs play different roles in the evolution from normal epithelial cells to malignant cells. Three DEGs ((FN1, CLU, and ANXA1)) related to prognosis were filtered, which may be regulated by DNA methylation, RNA methylation (m6A) and upstream transcription factors. The area under curve (AUC) of the diagnostic model based on 3-gene in the validation of our RNA-seq was 1. In the prognostic model based on 3-gene, the overall survival (OS) of high-risk patients was shorter. Combined with the clinical information of patients, a nomogram was constructed by using tumor size (pT) and risk score to quantify the prognostic risk. The age and tumor size of high-risk patients in the prognostic model were greater. In addition, the increase of tumor mutation burden (TMB) and diversity of T cell receptor (TCR), and the decrease of CD8+ T cells in high-risk group suggest the existence of immunosuppressive microenvironment. Conclusion: We applied the scRNA-seq pipeline to focus on epithelial cells in PTC, simulated the process of tumor evolution, and revealed a prognostic prediction model based on 3 genes, which is related to tumor immune microenvironment.

Quantitative Scintigraphy Evaluated the Relationship between 131I Therapy and Salivary Glands Function in DTC Patients: A Retrospective Analysis.

Purpose: Quantitative scintigraphy to evaluate salivary gland function changes in patients with differentiated thyroid cancer (DTC) after iodine-131 (131I) treatment. Methods: A total of 458 patients with DTC grouped by sex and age were included. Salivary gland scintigraphy was performed to evaluate salivary gland function before and after 131I treatment. The uptake fraction (UF), uptake index (UI), and excretion fraction (EF) of two pairs of parotid glands and submandibular glands were measured and compared. The Chi-square test was conducted according to function impairment count. Results: Salivary gland function in different age groups and sexes were quite different, especially for women <55 years old, who had decreased UF, UI, and EF of all four glands without basal injury. The secretion or uptake function of some salivary glands with basic function impairment before 131I treatment was increased after iodine treatment. Only a small percentage of males showed reduced functional parameters after several treatments. The most significant difference in the count of impairment for the four salivary glands were the first and third examinations, which was more evident in women. The submandibular gland had the most significant reduction in uptake. Conclusion: Changes in salivary gland function are more common in young females being treated for DTC. Impairment of salivary gland function is correlated with the number of treatments and the cumulative dose of 131I. Some salivary gland functions impaired before 131I treatment were enhanced in the early treatment.

Central Compartment Lymph Nodes Have Distinct Metastatic Patterns in Different Age Groups.

BACKGROUND AND PURPOSE: Central compartment lymph node metastasis (CLNM) is a manifestation of tumor aggressiveness and an indicator of tumor prognosis. The purpose of this study was to construct a nomogram for evaluating CLNM patterns in papillary thyroid carcinoma (PTC) in different age groups. METHOD: A total of 907 patients diagnosed with PTC from August 2014 to December 2018 were enrolled. A nomogram illustrating CLNM was generated using the results of multivariate logistic regression analysis. RESULTS: According to the best Youden index, we set the cut-off age at 45 years. Multivariate logistic regression analysis showed that in patients aged <45 years, large tumor size (P<0.05), extra-thyroid extension (P<0.05) and thyroglobulin level >40 ng/ml (OR=2.985, 95% CI 1.379-6.462; P<0.05) were independent risk factors; meanwhile, Hashimoto's thyroiditis (OR=0.532, 95% CI 0.324-0.874; P<0.05) was a protective factor of CLNM. In the subgroup with age ≥45 years, large tumor size (P<0.05), extra-thyroid extension (P<0.05), unclear margin (OR=1.604, 95% CI 1.065-2.416; P<0.05), male gender (OR=2.009, 95% CI 1.257-3.212; P<0.05) were independent risk factors for CLNM. In the subgroup with age <45 years, an area under the curve (AUC) of 0.729 (95% CI 0.680-0.777); P<0.05) was obtained. In the ≥45 years subgroup, the AUC was 0.668 (95% CI 0.619-0.716; P<0.05). CONCLUSION: CLNM of PTC in different age groups may have distinct patterns. Based on the potential risk factors for CLNM in patients with different age stratification, a user-friendly predictive model was established.

SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation.

TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment.

Urinary iodine concentration and radioactive iodine therapeutic response in patients with differentiated thyroid cancer.

Aim: Urinary iodine concentration (UIC) may assess radioactive iodine ablation. Materials & methods: According the 2015 American Thyroid Association guidelines, patients were categorized into low- to intermediate-risk or high-risk groups. The iodine concentration in the morning urine specimens was measured by the ceric ion-arsenious acid method. Results: In the low- to intermediate-risk group (113 cases), nonexcellent response (non-ER) was associated with higher UIC, higher UIC subgroups (p < 0.05), higher pre-ablative stimulated thyroglobulin levels (p < 0.01). In the high-risk group (68 cases), the non-ER rate was higher in the higher pre-ablative stimulated thyroglobulin group (p < 0.01), but not significantly different between the UIC and UIC subgroups (p > 0.05). Conclusion: The non-ER rate was related to UIC in the low- to intermediate-risk group; however, UIC did not affect the non-ER rate in the high-risk group.

Identification of a Six Gene Prognosis Signature for Papillary Thyroid Cancer Using Multi-Omics Methods and Bioinformatics Analysis.

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. PTC is typically curable with an excellent survival rate; however, some patients experience disease recurrence or death. This study aimed to discover potential key genes and signaling pathways of PTC, which could provide new insights for thyroid lesions. Four GEO microarray datasets were integrated to screen for candidate genes involved in PTC progression. A total of 164 upregulated and 168 downregulated differentially expressed genes (DEGs) were screened. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes were used in pathway enrichment analyses for DEGs. A protein-protein interaction network was then built and analyzed utilizing STRING and Cytoscape, followed by the identification of 13 hub genes by cytoHubba. CDH3, CTGF, CYR61, OGN, FGF13, and CHRDL1 were selected through survival analyses. Furthermore, immune infiltration, mutations and methylation analysis indicated that these six hub genes played vital roles in immune surveillance and tumor progression. ROC and K-M plots showed that these genes had good prognostic values for PTC which was validated by TCGA dataset. Finally, GSEA for a single hub gene revealed that each candidate hub gene had close associations with PTC development. These findings provided new insights into PTC pathogenesis and identified six candidate gene prognosis signature for PTC.

Identification of markers associated with brain metastasis from breast cancer through bioinformatics analysis and verification in clinical samples.

BACKGROUND: Brain metastasis from breast cancer (BC) is an important cause of BC-related death. The present study aimed to identify markers of brain metastasis from BC. METHODS: Datasets were downloaded from the public databases Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Weighted gene co-expression network analysis (WGCNA) was performed to identify metastasis-associated genes (MAGs). Least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression models were constructed for screening key MAGs. Survival analysis and receiver operating characteristic (ROC) curves were used for evaluating the prognostic value. The factors associated with tumor metastasis were integrated to create a nomogram of TCGA data using R software. Gene Set Enrichment Analyses (GSEA) was performed for detecting the potential mechanisms of identified MAGs. Immunohistochemistry (IHC) was used to verify the expression of the key genes in clinical samples. RESULTS: The genes in 2 modules were identified to be significantly associated with metastasis through WGCNA. LASSO Cox proportional hazards regression models were constructed successfully. Subsequently, a clinical prediction model was constructed, and a nomogram was mapped, which had better sensitivity and specificity for BC metastasis. Two key genes, discs large homolog 3 (DLG3) and growth factor independence 1 (GFI1), were highly expressed in clinical samples, and the expression of these 2 genes was associated with patients' survival time. CONCLUSIONS: We successfully constructed a clinical prediction model for brain metastasis from BC, and identified that the expression of DLG3 and GFI1 were strongly associated with brain metastasis from BC.

Establishment and validation of a nomogram model for predicting the survival probability of differentiated thyroid carcinoma patients: a comparison with the eighth edition AJCC cancer staging system.

PURPOSE: This study aimed to develop a clinically predictive nomogram model to predict the survival probability of differentiated thyroid carcinoma patients and compare the value of this model with that of the eighth edition AJCC cancer staging system. METHODS: We selected 59,876 differentiated thyroid carcinoma patients diagnosed between 2004 and 2015 from the SEER database and separated those patients into a training set (70%) and a validation set (30%) randomly. We used Cox regression analysis to build the nomogram model (model 1) and the eighth edition AJCC cancer staging model (model 2). Then we compared the predictive accuracy, discrimination, and clinical usage of both models by calculating AUC (Area under the curve), C-index, as well as analyzing DCA (Decision Curve Analysis) performance respectively. RESULTS: AUCs of all predicted time points (12-month, 36-month, 60-month, and 120-month) of model 1 were 0.933, 0.913, 0.879, and 0.868 for the training set; 0.933, 0.926, 0.916, and 0.894 for the validation set. As for model 2, data were 0.938, 0.906, 0.866, and 0.847 for the training set; 0.924, 0.925, 0.912, and 0.867 for the validation set. C-indices of model 1 were higher than those of model 2 (0.923 vs. 0.918 for the training set, 0.938 vs. 0.930 for the validation set). DCA comparison showed that the net benefit of model 1 was bigger when comparing with that of model 2. CONCLUSIONS: Model 1 provided with both better predictive accuracy and clinical usage compared with those of model 2 and might be able to predict the survival probability of differentiated thyroid carcinoma patients visually and accurately with a higher net benefit.

Integrated bioinformatics analysis for the identification of key genes and signaling pathways in thyroid carcinoma.

Thyroid carcinoma (TC) is one of the most common types of endocrine neoplasm with poor prognosis due to its aggressive behavior. Biomarkers for early diagnosis and prevention of TC are in urgent demand. By using a bioinformatics analysis, the present study aimed to identify essential genes and pathways associated with TC. First, the GSE27155 and GSE50901 expression profiles were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were obtained using the two microarray datasets and further subjected to integrated analysis. A gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed 45 common DEGs in the two datasets. GO and KEGG pathway analysis indicated that the biological functions of the DEGs included protein binding, cardiac muscle cell potential involved in contraction, aldehyde dehydrogenase activity, the TGF-ß receptor signaling pathway and the canonical Wnt signaling pathway. A protein-protein interaction network was also constructed and visualized to display the nodes of the top 9 up- and 36 downregulated common DEGs. The integrated bioinformatics analysis indicated that potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) was the most significantly upregulated DEG. The transcriptional levels of KCNJ2 were confirmed to be elevated in TC tissues compared with those in normal tissues using reverse transcription-quantitative PCR analysis. Furthermore, the expression level of KCNJ2 was significantly associated with the 5-year survival rate of patients with TC, which was determined using the Kaplan-Meier method. In TC cell lines, KCNJ2 was also upregulated as compared with that in a normal control cell line. Finally, small interfering RNA was used to knock down the expression of KCNJ2, which was demonstrated to inhibit cell proliferation, migration and invasion, while increasing apoptosis in TC cells. In conclusion, in the present study, KCNJ2 was screened as an oncogene with a crucial role in TC development and progression and may represent a promising candidate biomarker and therapeutic target for TC.

T Cell Receptor Beta-Chain Profiling of Tumor Tissue, Peripheral Blood and Regional Lymph Nodes From Patients With Papillary Thyroid Carcinoma.

Objective: To study the characteristics of the T cell receptor (TCR) repertoire in cancer tissue, peripheral blood and regional lymph nodes (LNs) from patients with papillary thyroid carcinoma (PTC). Methods: PTC tissue, peripheral blood mononuclear cells (PBMCs) and regional LNs of six patients with papillary thyroid carcinoma were harvested. T cell receptor beta-chain (TCRß) profiling was performed though high-throughput sequencing (HTS), and IMonitor, MiXCR and VDJtools were used to analyze the characteristics of the TCR repertoire. Results: The results of IMonitor and those of MiXCR and VDJtools were very similar. The unique CDR3 of TCRß from LNs was higher than that of PBMCs, and the CDR3 of TCRß from LNs was higher than that of PTC tissue. Shannon's diversity index, D50, inverse Simpson index_mean and normalized Shannon's diversity index_mean of CDR3 from LNs were higher than those of PTCs and PBMCs. The HEC (high expansion clones) rate of CDR3 sequences at the amino acid level in PTC tissue was higher than that of PBMCs, which was higher than that of LNs. The V-J HEC rate of CDR3 was highest in PTC tissue, followed by PBMCs and LNs. Conclusion: TCR CDR3 profiling showed differences among and within the PBMCs, PTC tissues and regional LNs of PTC, including unique CDR3, CDR3 HEC at the amino acid level, CDR3 V-J HEC at the amino acid level, Shannon's diversity index and D50. The TCRß repertoire of PTC tissue, peripheral blood and regional LNs of PTC provide a reference for further study of immunity mechanisms against PTC.