Prognostic subtypes of thyroid cancer was constructed based on single cell and bulk-RNA sequencing data and verified its authenticity.

There has been an increase in the mortality rate of thyroid cancer (THCA), which is the most common endocrine malignancy. We identified six distinct cell types in the THAC microenvironment by analyzing single-cell RNA sequencing (Sc-RNAseq) data from 23 THCA tumor samples, indicating high intratumoral heterogeneity. Through re-dimensional clustering of immune subset cells, myeloid cells, cancer-associated fibroblasts, and thyroid cell subsets, we deeply reveal differences in the tumor microenvironment of thyroid cancer. Through an in-depth analysis of thyroid cell subsets, we identified the process of thyroid cell deterioration (normal, intermediate, malignant cells). Through cell-to-cell communication analysis, we found a strong link between thyroid cells and fibroblasts and B cells in the MIF signaling pathway. In addition, we found a strong correlation between thyroid cells and B cells, TampNK cells, and bone marrow cells. Finally, we developed a prognostic model based on differentially expressed genes in thyroid cells from single-cell analysis. Both in the training set and the testing set, it can effectively predict the survival of thyroid patients. In addition, we identified significant differences in the composition of immune cell subsets between high-risk and low-risk patients, which may be responsible for their different prognosis. Through in vitro experiments, we identify that knockdown of NPC2 can significantly promote thyroid cancer cell apoptosis, and NPC2 may be a potential therapeutic target for thyroid cancer. In this study, we developed a well-performing prognostic model based on Sc-RNAseq data, revealing the cellular microenvironment and tumor heterogeneity of thyroid cancer. This will help to provide more accurate personalized treatment for patients in clinical diagnosis.

Serum deprivation response functions as a tumor suppressor gene in papillary thyroid cancer.

The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.

An Online Model for Central Lymph Node Metastases in Papillary Thyroid Carcinoma With BRAF V600E Mutation.

OBJECTIVE: To construct a predictive model to direct the dissection of the central lymph nodes in papillary thyroid cancer (PTC) with BRAF V600E mutation by identifying the risk variables for central lymph node metastases (CLNM). METHODS: Data from 466 PTC patients with BRAF V600E mutations underwent thyroid surgery was collected and analyzed retrospectively. For these patients, we conducted univariate and multivariate logistic regression analysis to find risk variables for CLNM. To construct a nomogram, the independent predictors were chosen. The calibration, discrimination, and clinical utility of the predictive model were assessed by training and validation data. RESULTS: CLNM was present in 323/466 PTC patients with BRAF V600E mutations. By using univariate and multivariate logistic regression, we discovered that gender, age, tumor size, multifocality, and pathological subtype were all independent predictors of CLNM in PTC patients with BRAF V600E mutations. A predictive nomogram was created by combining these variables. In both training and validation groups, the nomogram demonstrated great calibration capacities. The training and validation groups' areas under the curve (AUC) were 0.772 (specificity 0.694, sensitivity 0.728, 95% CI: 0.7195-0.8247) and 0.731 (specificity 0.778, sensitivity 0.653, 95% CI: 0.6386-0.8232) respectively. According to the nomogram's decision curve analysis (DCA), the nomogram might be beneficial. As well, an online dynamic calculator was developed to make the application of this nomogram easier in the clinic. CONCLUSION: An online nomogram model based on the 5 predictors included gender, age, pathological subtype, multifocality, and tumor size was confirmed to predict CLNM and guide the central lymph nodes dissection in PTC patients with BRAF V600E mutations.

Hashimoto's thyroiditis, microcalcification and raised thyrotropin levels within normal range are associated with thyroid cancer.

BACKGROUND: To confirm whether clinical and biochemical parameters or Hashimoto's thyroiditis (HT) could predict the risks of malignancy among subjects who underwent thyroidectomy, as well as to determine the influence of HT on the biological behavior of papillary thyroid cancer (PTC). METHODS: A total of 2,052 patients who underwent initial thyroidectomy were enrolled between June 2006 and August 2008. Serum free T4, free T3, thyrotropin (TSH), thyroglobulin, thyroglobulin antibody, antimicrosomal antibody, tumor-associated status, and thyroid disorders were documented. RESULTS: Binary logistic regression analysis was performed to define the risk predictors for thyroid cancer. Finally, calcification, HT, TSH, and age, were entered into the multivariate model. Multivariate logistic regression analysis revealed the risk of thyroid cancer increases in parallel with TSH concentration within normal range, and the risk for malignancy significantly increased with serum TSH 1.97-4.94 mIU/L, compared with TSH less than 0.35 mIU/L (OR = 1.951, 95% CI = 1.201-3.171, P = 0.007). Increased risks of thyroid cancer were also detected among the patients with HT (OR = 3.732, 95% CI = 2.563-5.435), and microcalcification (OR = 14.486, 95% CI = 11.374-18.449). The effects of HT on the aggressiveness of PTC were not observed in extrathyroidal invasion (P = 0.347), capsular infiltration (P = 0.345), angioinvasion (P = 0.512), and lymph node metastases (P = 0.634). CONCLUSIONS: The risk of malignancy increases in patients with higher level TSH within normal range, as well as the presence of HT and microcalcification. No evidence suggests that coexistent HT alleviates the aggressiveness of PTC.

Identification of a four-miRNA signature predicts the prognosis of papillary thyroid cancer.

BACKGROUND: In recently diagnosed patients with thyroid cancer, papillary thyroid cancer (PTC), as the most common histological subtype, accounts for 90% of all cases. Although PTC is known as a relatively adolescent malignant disease, there still is a high possibility of recurrence in PTC patients with a poor prognosis. Therefore, new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) have broad application prospects as diagnostic biomarkers in cancer. AIM: To explore novel markers consisting of miRNA-associated signatures for PTC prognostication. METHODS: We obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas. The patients were randomly assigned to either a training or testing cohort. RESULTS: We discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues, which contained 172 up-regulated and 65 down-regulated miRNAs. The evaluation of differently expressed miRNAs was conducted using our risk score model. We then successfully generated a four-miRNA potential prognostic signature [risk score = (-0.001 × hsa-miR-181a-2-3p) + (0.003 × hsa-miR-138-5p) + (-0.018 × hsa-miR-424-3p) + (0.284 × hsa-miR-612)], which reliably distinguished patients from high and low risk with a significant difference in the overall survival (P < 0.01) and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts, respectively. Additionally, there was a trend indicated that high-risk patients had shorter relapse-free survival, although statistical significance was not reached (P = 0.082) in our sequencing cohort. CONCLUSION: Our results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC. Accordingly, we would recommend more radical therapy and closer follow-ups for high-risk groups.

Prevalence and impact of non-alcoholic fatty liver disease in patients with papillary thyroid carcinoma.

PURPOSE: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Non-alcoholic Fatty Liver Disease (NAFLD) was possibly among the risk factors for thyroid carcinoma. It is uncertain whether NAFLD is associated with the aggressiveness of PTC. METHODS: We obtained data on patients with PTC who had undergone surgery at the First Affiliated Hospital of Wenzhou Medical University between January 2020 and February 2022. Pre-and post-operative data were obtained from electronic medical records and analyzed. Patients were split into two groups based on the NAFLD diagnostic criteria and compared using univariate and multivariate analysis through a logistic regression model. RESULTS: In all, 3468 patients with PTC were included in this study, of which 594 (17.1%) were diagnosed with NAFLD. NAFLD was found to be an independent risk factor for lymph node metastasis (OR = 1.285 95% CI: 1.052-1.570), incidence of BRAF V600E mutation (OR = 1.504, 95% CI: 1.148-1.972) and later tumor stage at diagnosis (OR = 2.310, 95% CI: 1.700-3.139) in PTC. The association mentioned above remained significant in subgroups of patients with Hashimoto's thyroiditis (HT), hypertension, diabetes (DM), high triglyceride (TG) levels, low levels of high-density lipoprotein-cholesterol (HDL-C), and high body mass index (BMI). In subgroup of female rather than male, NAFLD was an independent risk factor for lymph node metastasis (OR = 1.638 95% CI: 1.264-2.123), incidence of BRAF V600E mutation (OR = 1.973, 95% CI: 1.368-2.846) as well as later tumor stage (OR = 2.825, 95% CI: 1.964-4.063) in PTC. However, NAFLD was not a risk factor for the larger tumor size (>1 cm), extra-thyroidal extension (ETE), or multifocality in PTC. CONCLUSION: Our cross-sectional study indicated that there is a strong association of NAFLD with higher incidence of lymph node metastasis, higher incidence of BRAF V600E mutation and later TNM stage than non-NAFLD in females with PTC.

Factors predictive of papillary thyroid micro-carcinoma with bilateral involvement and central lymph node metastasis: a retrospective study.

BACKGROUND: The optimal resection extent for papillary thyroid microcarcinoma (PTMC) remains controversial. The objective of the study was to investigate risk factors of bilateral PTMC and central lymph node metastasis (CLNM) to guide surgical strategies for PTMC patients. METHODS: We retrospectively reviewed 211 PTMC patients who underwent total thyroidectomy (TT) and 122 clinical lymph node-negative (cN0) cases that underwent prophylactic central lymph node dissection (CLND) between 2010 and 2011. The frequency, pattern, and predictive factors for bilateral PTMC and CLNM in these patients were studied using univariate and multivariate analysis with respect to the following variables: age, gender, extrathyroidal extension (ETE), T stage, with Hashimoto thyroiditis (HT), tumor size and multifocality based on final pathology, and preoperative evaluation using ultrasonography (US). RESULTS: Fifty-four of 211 (25.6%) patients had bilateral PTMC. In multivariate analysis, multifocality (P < 0.001, OR = 23.900) and tumor size ≥7 mm (P = 0.014, OR = 2.398) based on US were independent predictive factors for bilateral PTMC which was also independently associated with multifocality (P < 0.001, OR = 29.657) and tumor size ≥7 mm (P = 0.005, OR = 2.863) based on final pathology. Among 122 cN0 patients who underwent prophylactic CLND, we found 49.2% of patients had CLNM. CLNM was independently associated with men, age <50 years and tumor size ≥7 mm based on final pathology or preoperative US. CONCLUSIONS: TT should be considered for PTMC patients who are found multifocality and tumor size ≥7 mm based on preoperative US. CLND need be considered in cN0 patients who are men, aged <50 years or tumor size ≥7 mm based on preoperative US.

Different distribution of breast ductal carcinoma in situ, ductal carcinoma in situ with microinvasion, and invasion breast cancer.

BACKGROUND: Breast ductal cancer in situ (DCIS) can recur or progress to invasive ductal cancer (IDC), and the interim stage include DCIS with microinvasion (DCIS-Mi). In this article, we attempt to study the study the differences of clinicopathological features, imaging data, and immunohistochemical-based subtypes among DCIS, DCIS-Mi, and IDC. METHODS: In this retrospective study, we attempt to compare the clinicopathological features, immunohistochemical results and imaging data of 866 patients (included 73 DCIS, 72 DCIS-Mi, and 721 IDC). RESULTS: Patients with DCIS and DCIS-Mi were younger than those with IDC (P = 0.007). DCIS and DCIS-Mi often happened in premenopausal women while IDC was opposite (P <0.001). The incidence of IDC with node-positive was significantly higher than it in DCIS and DCIS-Mi (P <0.001). We also observed that the Her2-positive was more often found in patients with pure DCIS compared to those with DCIS-Mi and DCIS-I (P <0.001). There was a significant difference between the four subgroups (Luminal-A, Luminal-B, ERBB2+, Basal-like) from DCIS, DCIS-Mi, and IDC (P <0.001). Basal-like patients were fewer than other subgroups in DCIS, DCIS-Mi, and IDC. The incidence of the first performance of ultrasound (catheter winded and nodular mass) and mammography (nodular mass) had significantly difference among patients with DCIS, DCIS-Mi, and IDC (P <0.001). CONCLUSIONS: Different clinicopathological, immunohistochemical, and imaging features among DCIS, DCIS-Mi, and IDC indicate that they are distinct entities. A larger sample size is needed for further study.

Genetic landscape of breast cancer and mutation tracking with circulating tumor DNA in Chinese women.

Considerable efforts have been devoted to exploring the breast cancer mutational landscape to understand its genetic complexity. However, no studies have yet comprehensively elucidated the molecular characterization of breast tumors in Chinese women. This study aimed to determine the potential clinical utility of peripheral blood assessment for circulating tumor-derived DNA (ctDNA) and comprehensively characterize the female Chinese population's genetic mutational spectrum. We used Omi-Seq to create cancer profiles of 273 patients enrolled at The First Affiliated Hospital of Wenzhou Medical University. The gene landscape results indicate PIK3CA and TP53 as the most frequently detected genes, followed by ERBB2, in Chinese breast cancer patients. The accuracy of ERBB2 copy number variations in tissue/formalin-fixed and paraffin-embedded samples was 95% with 86% sensitivity and 99% specificity. Moreover, mutation numbers varied between different molecular cell-free DNA subtypes, with the basal-like patients harboring a higher number of variants than the luminal patients. Furthermore, ratio changes in the max ctDNA allele fraction highly correlated with clinical response measurements, including cancer relapse and metastasis. Our data demonstrate that ctDNA characterization using the Omi-Seq platform can extend the capacity of personalized clinical cancer management.

Downregulated CDH3 decreases proliferation, migration, and invasion in thyroid cancer.

BACKGROUND: Placental-Cadherin (CDH3), a cell adhesion molecule, is associated with the function of cells to bind with other cells and the extracellular matrix (ECM). CDH3 is highly expressed in many malignancies, and has been proved it could be a serum marker to monitor colorectal cancer, but the CDH3 expression levels in thyroid cancer is still not clear. In this article, we will illuminate the correlation between CDHs expression and thyroid cancer. MATERIALS AND METHODS: We analyzed the level of CDH3 expression in 60 pair of tissue samples (contrast thyroid cancer tissues with adjacent normal thyroid tissues) by Real-time PCR, and TCGA data portal. After that, we transfected small interfering RNA to silence CDH3 in thyroid cancer cell lines (KTC-1 and BCPAP) and confirmed the function of CDH3 by performed colony formation, migration, invasion, cell counting kit-8 and apoptosis assays. RESULTS: CDH3 was upregulated in thyroid cancer tissues compared to the adjacent normal tissues (T:N=71.87±39.88:5.35±5.91, P<0.0001) and TCGA (T:N=19.43±13.82:1.22±1.33, P<0.0001). In thyroid cell lines (KTC-1 and BCPAP) experiments showed that downregulated CDH3 inhibited proliferation, migration, and invasion. Meanwhile, inhibited CDH3 expression could upregulate E-cadherin, downregulated N-cadherin, which may control invasion and migration. CONCLUSION: Thyroid cancer cells CDH3 expression levels is a correlation with its ability to grow, migrate and invade.

Quality assurance for interventional pain management procedures in private practice.

BACKGROUND: A recent study has indicated that quality assurance for interventional pain management procedures (IPMPs) can be achieved in university pain clinics. However, the issue of quality assurance for IPMPs in private practice has not yet been addressed. OBJECTIVE: This study was designed to monitor the quality of IPMPs in a private pain practice in north Florida. METHODS: From November 2005 to July 2006, we monitored the quality of IPMPs in a private pain practice in north Florida. Questionnaires regarding degree of pain relief, patient satisfaction, and complications were handed to patients immediately after the completion of each IPMP. Follow-up phone calls were also made to patients 1 day after the IPMPs. RESULTS: A total of 771 (male: 249, female: 522) patients with a mean age of 58.1 years participated in the study. Office-based IPMPs included lumbar and cervical epidural steroid injections, lumbar and cervical facet joint blocks, selective nerve root blocks, lumbar and cervical sympathetic nerve blocks, sacroiliac joint injection, and large joint injections. Seven-hundred patients (90.8%) reported various degrees of pain relief immediately following IPMPs. Average pain score decreased by 4.3 on a 0 to 10 scale (p=<0.001). Number needed to be treated (NNT) to reach 50% or more pain relief immediately after IPMPs was 1.4. Six-hundred ninety-two (89.7%) patients were satisfied or very satisfied with the results of IPMPs. Sixty-two patients (8%) developed headaches after IPMPs, which lasted from 30 minutes to 4 days. None of these patients required a blood patch. Five patients developed moderate vasovagal responses during IPMPs, in which their heart rates decreased to <45/min, BP <90/60mmHg. The IPMPs were aborted immediately. All of these patients recovered uneventfully within a few minutes. No other serious adverse events were reported. CONCLUSIONS: The results of the current study suggest that high quality private interventional pain programs with high efficacy, high patient satisfaction, and low complication rates can be achieved through appropriate staff training, proper monitoring of patients during IPMPs, and adequate handling of patients after the IPMPs.

Underexpression of INPPL1 is associated with aggressive clinicopathologic characteristics in papillary thyroid carcinoma.

PURPOSE: To study the relationship between INPPL1 gene and clinicopathologic characteristics of papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: INPPL1 expression in PTCs was tested by quantitative real-time reverse transcription PCR. The Cancer Genome Atlas (TCGA) RNA-seq data and our mRNA data were used to analyze and reveal the relationship between INPPL1 and aggressive clinicopathologic characteristics of PTC. RESULTS: When compared to normal thyroid tissues, INPPL1 was significantly downregulated in PTC tissues, as revealed by our data and TCGA data. INPPL1 underexpression was remarkably related to aggressive clinicopathologic characteristics such as lymph node metastasis (LNM), histological type, tumor size, mulitifocality, and disease stage in TCGA data. Meanwhile, LNM was confirmed to be associated with underexpression of INPPL1 in our data. In addition, logistic analysis clearly showed that underexpression of INPPL1 was an independent factor for LNM in PTC. CONCLUSION: INPPL1 may be a novel tumor suppressor gene in PTC, which was significantly correlated with aggressive clinicopathologic characteristics, especially LNM.

CLDN10 is Associated with Papillary Thyroid Cancer Progression.

The incidence of thyroid cancer is staying at a high level. Claudin family is a skelemin contacting with the intercellular junction and can keep a dynamic balance between cells. Recently, many types of research indicated that the expression level of claudins is closely related to various cancer types and they can be novel diagnostic markers. For instance, Claudin-10(CLDN10) is the high expression in primary hepatocellular carcinoma, papillary thyroid cancer (PTC) and so on. But the biological role and function of CLDN10 in PTC are unclear. In our study, we measured the expression of CLDN10 in human normal tissues and matched PTC tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and this observation was consistent with that in the TCGA cohort. We discovered that high expression of CLDN10 was correlated with lymph node metastasis, age and Histological type in TCGA cohorts. Kaplan-Meier analysis showed that patients with higher CLDN10 expression had a worse overall survival. In vitro, CLDN10 could promote cellular proliferation, migration, and invasion in PTC cell lines. In a word, CLDN10 is a functionally gene facilitating tumorgenesis in PTC and acts as an oncogene in PTC.

Diagnosis and minimally invasive treatment of lumbar discogenic pain--a review of the literature.

Diagnosis and treatment of lumbar discogenic pain due to internal disc disruption (IDD) remains a challenge. It accounts for 39% of patients with low back pain. The mechanism of discogenic pain remains unclear and its clinical presentation is atypical. Magnetic resonance imaging (MRI) can find high-intensity zone as an indirect indication of IDD. However, relative low sensitivity (26.7% to 59%) and high false-positive (24%) and false-negative (38%) rates reduce the value of MRI in screening for the existence of painful IDD. Provocative discography can provide unique information about the pain source and the morphology of the disc. It may also provide information for selecting appropriate treatment for the painful annular tear. Adjunctive therapies, including nonsteroidal anti-inflammatory drugs, physical therapy, rehabilitation, antidepressants, antiepileptics, and acupuncture, have been used for low back pain. The value of these treatments for discogenic pain is yet to be established. Intradiscal steroid injection has not been proved to provide long-term benefits. Intradiscal electrothermal therapy may offer some pain relief for a group of well-selected patients. No benefits have been found for the intradiscal radiofrequency thermocoagulation. A block in the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Disc cell transplantation is in the experimental stage. It has the potential to become a useful tool for the prevention and treatment of discogenic pain. Minimally invasive treatments provide alternatives for discogenic pain with the appeal of cost-effectiveness and, possibly, less long-term side effects. However, the value of most of these therapies is yet to be established. More basic science and clinical studies are needed to improve the clinical efficacy of minimally invasive treatments.

Quality assurance for interventional pain management procedures.

BACKGROUND: Over the last decade various guidelines for quality assurance in pain medicine have been published for cancer pain, acute postoperative pain and other pain conditions. However, quality assurance for interventional pain management procedures has yet to be addressed. An interventional pain program should at least evaluate 1) efficacy of pain relief; 2) complication rate; and 3) patient satisfaction. OBJECTIVE: This study was designed to monitor the quality of interventional pain management procedures in a university teaching hospital. STUDY DESIGN: A prospective survey. METHODS: From January 1, 2004, to June 30, 2004, the quality of interventional pain management procedures in a university teaching hospital in Miami, Florida was monitored. Questionnaires assessing immediate pain relief, patient satisfaction, and complications were provided to each patient and physician immediately after completion of each procedure. Data was collected before patients were discharged. RESULTS: A total of 566 patients with a mean age of 52.9 years participated in the survey. Interventional pain management procedures included epidural steroid injections, facet joint blocks, transforaminal epidural injections, sympathetic nerve blocks, lumbar discography, nucleoplasty, percutaneous disc decompression, spinal cord stimulator trial, and intravenous regional blocks, etc. Among 528 patients who reported their pain scores before and after procedures, 487 (92%) patients reported various degrees of pain relief immediately following their procedures. The average pain score decreased 4.7 on a o to 10 scale after treatment (p < 0.001). No major complications were reported for this group of patients. Among 442 patients who answered the question regarding satisfaction, 406 (91.8%) were satisfied, or highly satisfied, with the immediate outcome of their procedures. CONCLUSION: The results of the current study indicate that quality assurance of interventional pain management procedures in terms of immediate pain relief following the procedure, low complication rate, and high patient satisfaction can be achieved through application of a quality assurance program.

Next-generation sequence detects ARAP3 as a novel oncogene in papillary thyroid carcinoma.

PURPOSE: Thyroid cancer is the most frequent malignancies of the endocrine system, and it has became the fastest growing type of cancer worldwide. Much still remains unknown about the molecular mechanisms of thyroid cancer. Studies have found that some certain relationship between ARAP3 and human cancer. However, the role of ARAP3 in thyroid cancer has not been well explained. This study aimed to investigate the role of ARAP3 gene in papillary thyroid carcinoma. METHODS: Whole exon sequence and whole genome sequence of primary papillary thyroid carcinoma (PTC) samples and matched adjacent normal thyroid tissue samples were performed and then bioinformatics analysis was carried out. PTC cell lines (TPC1, BCPAP, and KTC-1) with transfection of small interfering RNA were used to investigate the functions of ARAP3 gene, including cell proliferation assay, colony formation assay, migration assay, and invasion assay. RESULTS: Using next-generation sequence and bioinformatics analysis, we found ARAP3 genes may play an important role in thyroid cancer. Downregulation of ARAP3 significantly suppressed PTC cell lines (TPC1, BCPAP, and KTC-1), cell proliferation, colony formation, migration, and invasion. CONCLUSION: This study indicated that ARAP3 genes have important biological implications and may act as a potentially drugable target in PTC.

BRAF and TERT promoter mutations in the aggressiveness of papillary thyroid carcinoma: a study of 653 patients.

The role of telomerase reverse transcriptase (TERT) gene promoter mutations in the aggressiveness of papillary thyroid cancer (PTC) remains to be further investigated. Here we examined the relationship of TERT promoter mutations and BRAF V600E with the clinicopathological features of PTC in 653 patients. Sanger sequencing of genomic DNA from primary PTC tumors was performed for mutation detection and genotype-clinicopathological correlation of the tumor was analyzed. BRAF V600E and TERT promoter mutations were found in 63.7% (416 of 653) and 4.1% (27 of 653) of patients, respectively; the latter became 9.8% when only tumors ≥ 1.5 cm were analyzed. TERT promoter mutations occurred more frequently in BRAF mutation-positive cases compared to wild-type cases, being 5.3% in the former versus 2.1% in the latter (P = 0.050). BRAF and TERT promoter mutations were each significantly associated with high-risk clinicopathological features of PTC, such as old patient age, large tumor size, extrathyroidal invasion, capsular invasion, and advanced disease stages. Coexistence of BRAF V600E and TERT promoter mutations was particularly associated with high-risk clinicopathological features, as exemplified by extrathyroidal invasion seen in 54.5% (12/22) of patients harboring both mutations versus 9.9% (23/232) of patients harboring neither mutation (P < 0.001). Thus, this study, the largest on TERT mutation so far, demonstrates a significant role of BRAF V600E and TERT promoter mutations in the aggressiveness of PTC, which is particularly robust and cooperative when the two mutations coexist. These results, together with previous studies, establish a significant role of these mutations in the aggressiveness of PTC.

A prospective crossover comparison study of the single-needle and multiple-needle techniques for facet-joint medial branch block.

BACKGROUND AND OBJECTIVES: Medial branch blocks have been widely described in the literature as a diagnostic tool for facet joint pain. Recently, a new "single-needle' technique was described that is purported to be equally accurate, and in some respects, superior to the standard multiple-needle technique. To date, no studies have been performed that compared these 2 techniques. METHODS: In a multicenter setting, 24 subjects underwent 2 separate diagnostic medial-branch blocks in a randomized, single-blind crossover comparison of the single-needle and multiple-needle techniques. Multiple variables were compared between the 2 techniques, including procedure-related discomfort, post-procedure pain relief, volume of local anesthetic required, accuracy as determined by final needle position and contrast-media spread, and time needed to perform the procedure. RESULTS: In this pilot study, the single-needle technique resulted in less procedure-related pain (P = .0003), required less superficial local anesthesia (P =.0006), and took less time to complete (P < .0001) than did the multiple-needle approach. With regard to final needle position, contrast spread, and post-procedure pain relief (P = .8), no differences were noted between the 2 techniques. CONCLUSIONS: Our results indicate that the single-needle technique takes less time to perform and causes less patient discomfort than does the standard technique but provides the same degree of accuracy. More studies with larger sample sizes are needed to corroborate these results and explore the effect the single-needle approach has on the rate of false-positive medial branch blocks.