A pan-cancer analysis of the prognosis and immune infiltration of eEF1A2 and its potential function in thyroid carcinoma.

Purpose: Eukaryotic translation elongation factor 1α2 (eEF1A2) promotes tumour progression in various cancers. We performed a pan-cancer analysis of eEF1A2 and explored its role in thyroid carcinoma (THCA). Methods: Databases from The Cancer Genome Atlas (TCGA), the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and the Human Protein Atlas (HPA) were used to investigate the differential expression of eEF1A2 in pan-cancer. The pathological stage, prognostic characteristics, tumour microenvironment (TME), tumour mutational burden (TMB), and microsatellite instability (MSI) were analysed in diverse tumours with different expression levels of eEF1A2. The expression levels in papillary thyroid carcinoma (PTC) and its specific role in cell proliferation, migration, invasion, and cell glycolysis in PTC cells were verified by quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry, cell counting kit-8, colony formation, wound healing, Transwell assay, and lactate acid and glucose assays.Results:eEF1A2 was differentially expressed in various malignant tumour tissues compared to control tissues and was associated with poor pathological stage and prognosis in most types of tumours. Moreover, eEF1A2 expression closely correlated with the infiltration of immunosuppressive cells, TMB, and MSI in some tumour types. Expression of eEF1A2 in PTC is higher than the para-carcinoma, and eEF1A2 downregulation suppressed TPC-1 and BCPAP cell proliferation, migration, invasion, and glycolysis. Conclusion: Our study suggests that the expression of eEF1A2 is related to the prognosis and immune infiltration of some tumours and may be a predictor of prognosis and immunotherapy. eEF1A2 could promote malignant behaviour of PTC cells.

Transcription factor FOXP4 inversely governs tumor suppressor genes and contributes to thyroid cancer progression.

Objective: In recent decades, thyroid cancer (TC) has exhibited a rising incidence pattern. Elevated levels of the transcription factor FOXP4 have been strongly linked to the progression of diverse tumors; nevertheless, its specific role in thyroid cancer remains underexplored. The primary objective of this study was to elucidate the functions of FOXP4 and its associated target gene, FBXW7, in the context of thyroid cancer. Methods: FOXP4 and FBXW7 expression levels in TC tissues and cell lines were assessed through immunohistochemistry and RT-qPCR analyses. The functional aspects of FOXP4, including its effects on cell proliferation, migration capabilities, cell cycle regulation, and epithelial-mesenchymal transition (EMT), were investigated. Furthermore, the interaction between FOXP4 and FBXW7 was confirmed using chromatin immunoprecipitation (ChIP) assays. The impact of FBXW7 on FOXP4-mediated cellular phenotypes was subsequently examined. Additionally, the in vivo role of FOXP4 and FBXW7 in tumor growth was elucidated through the establishment of a murine tumor model. Results: Elevated levels of FOXP4 were observed in papillary carcinoma tissues, and patients exhibiting high FBXW7 levels showed a more favorable prognosis. KTC-1 cells displayed a concomitant increase in FOXP4 expression and decrease in FBXW7 expression. FOXP4 overexpression in these cells enhanced cell proliferation, migration capabilities, and EMT. The interaction between the FOXP4 protein and the FBXW7 promoter was confirmed, and the effects of FOXP4 were mitigated upon overexpression of FBXW7. Furthermore, knockdown of FOXP4 led to decelerated growth of transplanted tumors and increased FBXW7 levels within the tumors. Conclusion: The findings of the current study underscore the regulatory role of FOXP4 in the transcription of FBXW7 and establish a clear link between aberrations in FBXW7 expression and the manifestation of malignant phenotypes in highly aggressive TC cells.

Integrating US-guided FNAB, BRAFV600E mutation, and clinicopathologic characteristics to predict cervical central lymph-node metastasis in preoperative patients with cN0 papillary thyroid carcinoma.

BACKGROUND: The prevalence of cervical central lymph-node metastasis (CLNM) is high in patients with papillary thyroid carcinoma (PTC). There is considerable controversy surrounding the benefits of prophylactic central lymph-node dissection (pCLND) in patients with clinically negative central compartment lymph nodes (cN0). Therefore, it is crucial to accurately predict the likelihood of cervical CLNM before surgery to make informed surgical decisions. METHODS: Date from 214 PTC patients (cN0) who underwent partial or total thyroidectomy and pCLND at the Guizhou Provincial People's Hospital were collected and retrospectively analyzed. They were divided into two groups in accordance with cervical CLNM or not. Their information, including clinical characteristics, ultrasound (US) features, pathological results of fine-needle aspirations biopsy (FNAB), and other characteristics of the groups, was analyzed and compared using univariate and multivariate logistic regression analyses. RESULTS: A total of 214 patients were eligible in this study. Among them, 43.5% (93/214) of PTC patients had cervical CLNM, and 56.5% (121/214) did not. The two groups were compared using a univariate analyses, and there were no significant differences between the two groups in aspect ratio, boundary, morphology, component, and BRAFV600E (P > 0.05), and there were significant differences between gender, age, maximum tumor size, tumor location, capsule contact, microcalcifications, color Doppler flow imaging (CDFI), and Hashimoto's thyroiditis (HT) (P < 0.05). A multivariate logistic regression analysis was performed to further clarify the correlation of these indices. However, only age (OR = 2.455, P = 0.009), maximum tumor size (OR = 2.586, P = 0.010), capsule contact (OR = 3.208, P = 0.001), and CDFI (OR = 2.225, P = 0.022) were independent predictors of cervical CLNM. Combining these four factors, the area under the receiver-operating characteristic (ROC) curve for the joint diagnosis is 0.8160 (95% 0.7596-0.8725). Univariate analysis indicated that capsule contact (P = 0.001) was a possible predictive factor of BRAFV600E mutation. CONCLUSIONS: In conclusion, four independent predictors of cervical CLNM, including age < 45 years, tumor size > 1.0 cm, capsule contact, and rich blood flow, were screened out. Therefore, a comprehensive assessment of these risk factors should be conducted when designing individualized treatment regimens for PTC patients.

The essential role of forkhead box P4 (FOXP4) in thyroid cancer: a study related to The Cancer Genome Atlas and experimental data.

Objective: Thyroid cancer (THCA) is the most common endocrine cancer in the world. Although most patients with THCA have a good prognosis, the prognosis of those with THCA who have an extra-glandular invasion, vascular invasion, and distant metastasis is poor. Therefore, it is very important to find potential biomarkers that can effectively predict the prognosis and progression of highly aggressive THCAs. It has been identified that forkhead box P4 (FOXP4) may be a new biomarker for the proliferation and prognosis for tumor diagnosis. However, the expression and function of FOXP4 in THCA remain to be determined. Methods: In the present study, the function of FOXP4 in cells was investigated through the comprehensive analysis of data in The Cancer Genome Atlas and combined with experiments including immunohistochemistry (IHC), colony formation, Cell Counting Kit-8 assay, wound scratch healing, and transwell invasion assay. Results: In the present study, relevant bioinformatic data showed that FOXP4 was highly expressed in THCA, which was consistent with the results of the IHC and cell experiments. Meanwhile, 10 FOXP4-related hub genes were identified as potential diagnostic genes for THCA. It was found in further experiments that FOXP4 was located in the nucleus of THCA cells, and the expression of FOXP4 in the nucleus was higher than that in the cytoplasm. FOXP4 knockdown inhibited in vitro proliferation of the THCA cells, whereas overexpression promoted the proliferation and migration of THCA cells. Furthermore, deficiency of FOXP4 induced cell-cycle arrest. Conclusion: FOXP4 might be a potential target for diagnosing and treating THCA.

FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway.

Papillary thyroid carcinoma, also known as PTC, is one of the commonest malignancies in the endocrine system. Long non-coding RNAs (lncRNAs) in PTC could maintain proliferative signaling, induce therapeutic resistance, activate invasion and migration, and sustain stem cell-like characteristics. In this paper, results showed that lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) is downregulated in PTC tissues and cell lines. Patients in TCGA cohort with a higher FOXP4-AS1 expression showed a higher disease-free interval (DFI) rate, and the expression of FOXP4-AS1 is shown to be linked to the clinical stage, T stage, N stage, and extraglandular invasion condition of the TC patients. FOXP4-AS1 is localized in the cell cytoplasmic domain of PTC cells. Functionally, upregulated FOXP4-AS1 inhibited PTC cell proliferation, apoptosis, and migration, whereas it downregulated FOXP4-AS1-promoted progression of PTC. In vivo assay also confirmed the tumor inhibitory effect of FOXP4-AS1 in PTC growth. Mechanism analysis indicated that FOXP4-AS1 can play its functions by regulating the AKT signaling pathway, and AKT inhibitor treatment could attenuate the impact of FOXP4-AS1 on PTC progression. Furthermore, FOXP4-AS1 also negatively regulates the expression of its host gene FOXP4. Collectively, we showed that FOXP4-AS1 inhibited PTC progression although AKT signaling and FOXP4-AS1 plays a tumor-suppressor role in PTC tumorigenesis.

High expression of SEZ6L2 as an independent prognostic Indicator in thyroid carcinoma.

Background: Seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) is a type 1 transmembrane protein that is primarily expressed in the brain . In recent reports, SEZ6L2 has been found to be overexpressed in some cancers and can drive the progression of tumors. However, its function and mechanism in thyroid cancer remain unclear. Methods: In this article ,we searched for the SEZ6L2 expressions in Pan-cancer on TCGA (The Cancer Genome Atlas) and evaluated these data using the TIMER2 method. Then, the immunohistochemical score (IHC score) of SEZ6L2 in cancer tissue was collected in human protein mapping (HPA) data. And we used CIBERSORT to assess the association between the levels of SEZ6L2 expression and the number of various immune cells in papillary thyroid carcinoma (PTC) tissue. Finally, Gene Expression Omnibus (GEO) analyses, real-time quantitative polymerase chain reaction (qRT-PCR) of tissues, and immunohistochemical staining were used to detect the result. Results: The article illustrated that a large number of cancers had a higher expression of SEZ6L2 compared to the control tissues. And the immunohistochemical score (IHC score) of SEZ6L2 in cancer tissue was considerably elevated compared to that in normal tissues SEZ6L2 was elevated in thyroid carcinoma (THCA) tissue, besides, GEO analyses, qRT-PCR of tissues, and immunohistochemical staining were conducted to test the results. Finally, the Kaplan-Meier survival analysis illustrated that the increased expression of SEZ6L2 was correlated with a dismal prognosis-higher SEZ6L2 is associated with shorter survival. And the univariate analysis illustrated that T stage, SEZ6L2 and Pathologic stage were related to the overall survival (OS), multivariate analysis stated that elevated expression of SEZ6L2 was an independent risk factor that affected progression-free interval (PFI) (P<0.05). Consequently, we found that the expression of SEZ6L2 was correlated with tumor-infiltrating immune cells by TIMER. Conclusions: SEZ6L2 was upregulated in patients with THCA and that increased expression of SEZ6L2 was related with clinical progression and was regarded as an independent risk factor for PFI. In THCA patients, the expression of SEZ6L2 could be a significant prognostic factor, which is expected to be a prospective biomarker for THCA in the future.

Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1.

BACKGROUND Shikonin is a component of Chinese herbal medicine. The aim of this study was to investigate the effects of shikonin on cell migration of papillary thyroid cancer cells of the TPC-1 cell line in vitro and expression levels of the phosphate and tensin homolog deleted on chromosome 10 (PTEN) and DNA methyltransferase 1 (DNMT1) genes. MATERIAL AND METHODS The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the proliferation of TPC-1 papillary thyroid cancer cells, and the normal thyroid cells, HTori-3, in vitro. A transwell motility assay was used to analyze the migration of TPC-1 cells. Western blot was performed to determine the expression levels of PTEN and DNMT1 genes. A methylation-specific polymerase chain reaction (PCR) (MSP) assay was used to evaluate the methylation of PTEN. RESULTS Following treatment with shikonin, the cell survival rate of TPC-1 cells decreased in a dose-dependent manner; the inhibitory effects on HTori-3 cells were less marked. Shikonin inhibited TPC-1 cell migration and invasion in a dose-dependent manner. The methylation of PTEN was suppressed by shikonin, which also reduced the expression of DNMT1 in a dose-dependent manner, and increased the expression of PTEN. Overexpression of DNMT1 promoted the migration of TPC-1 cells and the methylation of PTEN. Levels of protein expression of PTEN in TPC-1 cells treated with shikonin decreased, and were increased by DNMT1 knockdown. CONCLUSIONS Shikonin suppressed the expression of DNMT1, reduced PTEN gene methylation, and increased PTEN protein expression, leading to the inhibition of TPC-1 cell migration.

[Diagnosis value of thyroid imaging reporting and data system in thyroid nodules].

OBJECTIVE: To explore the diagnostic value of the proposed thyroid imaging reporting and data system (TI-RADS) classification in thyroid nodules, and to investigate interobserver variability among different observers using TI-RADS classification for ultrasound. METHOD: We reviewed 667 thyroid nodules conventional ultrasound image data from 532 patients who were confirmed by Pathological diagnosis. Those ultrasound images were reviewed by 4 experienced sonographers who can independently assessed the sonographic characteristics and analyzed according to the TI-RADS classification. It is to assess the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the TI-RADS classification. The multirater kappa statistics were used to assess the interobserver agreement among different observers. RESULT: The overall sensitivity, specificity, negative predictive value (NPV) and Accuracy were 94%, 79%, 97% and 81%, respectively. Positive predictive values (PPVs) for categories 4 and 5 were 55% and 92%. There was substantial interobserver agreement for categories 3, 4B and 5 (Kappa = 0.62, 95% CI, 0.58-0.65), and was moderate agreement for category 4A (Kappa = 0.57) and 4B(Kappa = 0.60). CONCLUSION: The diagnostic criteria of TI-RADS for differentiating between benign and malignant thyroid nodules have a high diagnostic value. There was substantial interobserver agreement in different experienced sonographers. The TI-RADS diagnostic criteria have a high diagnostic value and has great practical value in making a proper and further treatment plan.

Universal Fluorescence Biosensor Platform Based on Graphene Quantum Dots and Pyrene-Functionalized Molecular Beacons for Detection of MicroRNAs.

A novel biosensor platform was developed for detection of microRNAs (miRNAs) based on graphene quantum dots (GQDs) and pyrene-functionalized molecular beacon probes (py-MBs). Pyrene was introduced to trigger specifically fluorescence resonance energy transfer (FRET) between GQDs and fluorescent dyes labeled on py-MBs, and the unique fluorescent intensity change produced a novel signal for detection of the target. The platform realized detection of miRNAs in a wide range from 0.1 nM to 200 nM with great discrimination abilities, as well as multidetection of different kinds of miRNAs, which paved a brand new way for miRNA detection based on GQDs.

Lamotrigine attenuates cerebral ischemia-induced cognitive impairment and decreases ß-amyloid and phosphorylated tau in the hippocampus in rats.

Lamotrigine (LTG) has shown benefits in animal models of cerebral ischemia, but the mechanism involved was not fully studied. This study was carried out to examine the effects of LTG on cognitive dysfunction, ß-amyloid1-42 accumulation, and tau protein hyperphosphorylation in the hippocampus of ischemic rats. Transient ischemic stroke was induced by middle cerebral artery occlusion. The Morris water maze test was used to evaluate the cognitive function of rats. We found that LTG significantly attenuated ischemia-induced cognitive deficits and decreased neuronal injury in the hippocampal CA1 zone. Moreover, LTG reduced ß-amyloid1-42 and phosphorylated tau (AT8) in the hippocampus after ischemia. These results suggested that the cognition-protective effects of LTG after cerebral ischemia might involve inhibition of toxic ß-amyloid accumulation and tau hyperphosphorylation in the hippocampus.

The Applications of Targeting Anti-Cancer Agents in Cancer Therapeutics.

Anti-cancer targeting drugs appear to be a new and powerful "weapon" for cancer therapies. These targeting drugs are directed against specific molecules that are over-expressed or where certain unique factors are aberrantly expressed either in cancer cells or in diseased cell sites. Compared with traditional chemotherapeutic drugs, these targeting drugs have the advantages of high specificity, efficacy and less side effects. Target therapy is a breakthrough and revolutionary advance in the field of cancer therapy. Tumor angiogenesis plays a key role in tumor growth and metastasis and the mutation of tyrosine kinases is also strongly associated with cancer progression. Thus, in this review, we will discuss the advances in the development of targeting anti-cancer drugs by narrowing it down to small molecule tyrosine kinase inhibitors, monoclonal antibodies against epidermal growth factor receptors belonging to the ErbB family of receptor tyrosine kinases and angiogenic inhibitors. It will also address concerns for drug resistance and adverse events.

[Study on the correlation between BRAF(V600E) mutation and lymphatic metastases in papillary thyroid cancer staged preoperativelv as N0].

OBJECTIVE: To study the prevalence of BRAF(V600E) mutations in small (≤ 2 cm) papillary thyroid carcinoma (PTC), explore the correlation with occult central nodal metastasis (CNM) of clinically-nodal negative (cN0) neck for small (≤ 2 cm) papillary thyroid carcinoma (PTC). METHOD: Primary tumor tissue (paraffin-embedded) from 72 patients with small (≤ 2 cm) cN0 PTC who underwent prophylactic central neck dissection (pCND) was tested for BRAF mutation. by nested PCR, the factors of lymph node metastasis such as clinicopathologic including tumor size, multifocality, extrathyroidal invasion, and BRAF mutations were analyzed. Prediction scores were generated using logistic regression models and BRAF was evaluated to see if it was a risk factor for CNM. RESULT: The prevalence of BRAF was 47.22% (34/72) while the rate of CNM was 36.11% (26/72). Univariate analysis showed that the risk factors of lymph node metastasis for cN0 PTC were significantly correlated with tumor size (P = 0.016), bilateral tumor (P = 0.010), multifocality (P = 0.026), extrathyroidal invasion (P = 0.024), and BRAF mutations (P = 0.041). Univariate analysis showed that tumor size (OR = 2.674, 95% CI = 1.702-3.997), multifocality (OR = 1.371, 95% CI = 1.065-2.087), extrathyroidal invasion (OR = 0.540, 95% CI = 0.396-0.794) and BRAF (OR = 1.647, 95% CI = 1.101-2.463) were risk predictors of CNM. CONCLUSION: The incidence of central neck micrometastatic disease is 36.11% in patients with PTC deemed N0 preoperatively by clinical examination and ultrasound of the neck lymph nodes and intraoperatively by inspection of the central compartment. The factors of high risk of CNM included tumor size, multifocality, extrathyroidal invasion, BRAF mutations. When a patient has the risk factors of lymph node metastasis should be electived prophylactic CCND.

[Clinical application of carbon nanoparticles labeled lymph node in cervical lymph node dissection with papillary thyroid cancer staged preoperatively as N0].

OBJECTIVE: To investigate the clinical application of carbon nanoparticles staining in cervical lymph node dissection on clinical neck lymph nodes the negative (cN0 period) thyroid papillary thyroid carcinoma (PTC). METHOD: This retrospective analysis comprised 100 papillary thyroid cancer patients who met inclusion criteria,and they were randomly divided into the nano-carbon group (50 cases) and control group (50 cases). They underwent lobectomy, subtotal thyroidectomy or total thyroidectomies and were given elective central compartment neck dissection (CCND). The number of detected lymph nodes in each group was summed, and pathological examination was conducted. The number of lymph nodes (dyedor not dyed) and the location of metastatic nodes were recorded separately. RESULT: In the nano-carbon group the average number of eliminated lymph nodes is significantly more than that of the control group(P<0.05). The metastasis lymph nodes in the nano-carbon group was higher than that in the control group(P<0.01). Among 100 cases, 2% had temporary vocal cord palsy, and 8% had temporary hypoparat hyroidism. No case of permanent vocal cord palsy or permanent hypocalcemia was observed. CONCLUSION: The dyed lymph nodes can be easily identified and can be used as a guide for lymphnodes dissection in papillary thyroid carcinoma operation.