Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase II trial.

OBJECTIVE: Glioblastomas are highly vascularized malignant tumors. We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor, anlotinib, for a newly diagnosed glioblastoma. METHODS: This multicenter, single-arm trial (NCT04119674) enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020. Patients underwent treatment with the standard STUPP regimen [fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w × 6 w (total = 54-60 Gy)] or radiotherapy plus continuous daily temozolomide (TMZ) (75 mg/m2 of body surface area/d, 7 d/w from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ (150-200 mg/m2 × 5 d during each 28-d cycle) plus anlotinib (8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy, 8 maximal cycles as adjuvant therapy, followed by maintenance at 8 mg/d. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). RESULTS: Thirty-three patients received the planned treatment. The median PFS was 10.9 months (95% CI, 9.9-18.7 months) and the 12-month PFS rate was 48.5%. The median OS was 17.4 months (95% CI, 14.5-21.1 months) and the 12-month OS rate was 81.8%. The most common AEs included hypertriglyceridemia [58% (n = 19)], hypoalbuminemia [46% (n = 15)], and hypercholesterolemia [46% (n = 15)] during concurrent chemoradiotherapy and leukopenia [73% (n = 24)], hypertriglyceridemia [67% (n = 22)], and neutropenia [52% (n = 17)] during adjuvant therapy. Five patients discontinued treatment due to AEs. HEG1 (HR, 5.6; 95% CI, 1.3-23.7; P = 0.021) and RP1L1 alterations (HR, 11.1; 95% CI, 2.2-57.2; P = 0.004) were associated with a significantly shorter PFS. CONCLUSIONS: Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity. HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

New progress in the treatment of diffuse midline glioma with H3K27M alteration.

Diffuse midline glioma with H3K27 M alteration is a primary malignant tumor located along the linear structure of the brain, predominantly manifesting in children and adolescents. The mortality rate is exceptionally high, with a mere 1 % 5-year survival rate for newly diagnosed patients. Beyond conventional surgery, radiotherapy, and chemotherapy, novel approaches are imperative to enhance patient prognosis. This article comprehensively reviews current innovative treatment modalities and provides updates on the latest research advancements in preclinical studies and clinical trials focusing on H3K27M-altered diffuse midline glioma. The goal is to contribute positively to clinical treatment strategies.

The Impact of Time Interval on Prognosis in Patients with Non-Small Cell Lung Cancer Brain Metastases After Metastases Surgery.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a prominent malignancy often linked to the development of brain metastases (BM), which commonly appear at diverse time intervals (TI) following the lung cancer diagnosis. This study endeavors to determine the prognostic significance of the time interval in patients with NSCLC who undergo BM surgery. Through this investigation, we aim to improve our understanding of the factors impacting the prognosis of BM cases originating from NSCLC. METHODS: We analyzed data from 74 patients (2011-2021) who underwent BM surgery at our institution. The relationship between various clinical, radiological, and histopathological factors, as well as TI and overall survival (OS), was examined. RESULTS: The median TI from initial NSCLC diagnosis to BM surgery was 19 months (range: 9-36 months). Notably, a shorter TI of less than 23 months was found to be independently associated with postoperative survival (adjusted odds ratio [aOR] 2.87, 95% confidence interval [CI] 1.03-8.02, P = 0.045). Additionally, a shorter TI was independently correlated with the absence of adjuvant chemotherapy for NSCLC (aOR 0.25, 95% CI 0.07-0.83, P = 0.023) and lack of targeted therapy (aOR 0.02, 95% CI 0.00-0.16, P < 0.001). Late-onset BM (TI ≥ 36 months) was observed in 15 cases (20.3%), in this subgroup, patients aged 60 years or older at the time of lung cancer diagnosis exhibited a significant independent correlation with late-onset BM (aOR 7.24, 95% CI 1.59-32.95, P = 0.011). NSCLC patients who underwent adjuvant chemotherapy displayed a notable correlation with late-onset BM (aOR 6.46, 95% CI 1.52-27.43, P = 0.011), while those who received targeted therapy also exhibited an independent association (aOR 2.27, 95% CI 1.70-3.03, P < 0.001). CONCLUSIONS: Multiple factors contribute to the variability in the onset interval of BM subsequent to NSCLC diagnosis. The occurrence of BM within TI < 23 months following the initial diagnosis of NSCLC was demonstrated as an independent factor associated with an unfavorable prognosis following BM surgery. Furthermore, patients with NSCLC who did not receive adjuvant chemotherapy and lacked targeted therapy were shown to have an elevated likelihood of developing BM after a long progression-free survival.

Erratum: CELF1 is Up-Regulated in Glioma and Promotes Glioma Cell Proliferation by Suppression of CDKN1B: Erratum.

[This corrects the article DOI: 10.7150/ijbs.11344.].

circRNA-SMO upregulates CEP85 to promote proliferation and migration of glioblastoma via sponging miR-326.

Circular RNAs (circRNAs) play an important role in cancer development by sponging microRNAs (miRNAs) to regulate the signaling axis. However, more comprehensive mechanisms of circRNAs in glioblastoma need to be elucidated. RT-qPCR was used to detect the expression levels of circRNA-SMO and miR-326. Dual-luciferase reporter assays were conducted to verify the interaction among circRNA-SMO, miR-326, and CEP85. Flow cytometric analysis was performed to detect apoptosis. Western blotting was used to determine the protein levels of the different molecules. Animal xenograft experiments were performed to evaluate the role of circRNA-SMO in vivo. CircRNA-SMO was upregulated in glioblastoma tissues and glioblastoma cells. CircRNA-SMO downregulation inhibited the viability and colony-forming ability of the glioblastoma cells. In addition, miR-326 was downregulated in glioblastoma cells, which was verified to sponge circRNA-SMO and interact with CEP85. Moreover, circRNA-SMO inhibition induced the elevation of miR-326 and apoptosis, accompanied by a decrease in CEP85. CircRNA-SMO knockdown-mediated tumor inhibition was prevented by an miR-326 inhibitor. Furthermore, circRNA-SMO inhibition inhibited tumor growth in vivo, accompanied by an increase in miR-326 and a decline in CEP85 in tumor tissues. Conclusions. CircRNA-SMO sponges miR-326 to promote glioblastoma proliferation and migration by upregulating CEP85 expression. This study clarified the role of circRNA-SMO in the development of glioblastoma, providing novel insights for its treatment.

Racial and regional disparities of triple negative breast cancer incidence rates in the United States: An analysis of 2011-2019 NPCR and SEER incidence data.

Objective: Triple negative breast cancer (TNBC) is a more aggressive subtype resistant to conventional treatments with a poorer prognosis. This study was to update the status of TNBC and the temporal changes of its incidence rate in the US. Methods: Women diagnosed with breast cancer during 2011-2019 were obtained from the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology and End Results (SEER) Program SEER*Stat Database which covers the entire population of the US. The TNBC incidence and its temporal trends by race, age, region (state) and disease stage were determined during the period. Results: A total of 238,848 (or 8.8%) TNBC women were diagnosed during the study period. TNBC occurred disproportionally higher in women of Non-Hispanic Black, younger ages, with cancer at a distant stage or poorly/undifferentiated. The age adjusted incidence rate (AAIR) for TNBC in all races decreased from 14.8 per 100,000 in 2011 to 14.0 in 2019 (annual percentage change (APC) = -0.6, P = 0.024). Incidence rates of TNBC significantly decreased with APCs of -0.8 in Non-Hispanic White women, -1.3 in West and -0.7 in Northeastern regions. Women with TNBC at the age of 35-49, 50-59, and 60-69 years, and the disease at the regional stage displayed significantly decreased trends. Among state levels, Mississippi (20.6) and Louisiana (18.9) had the highest, while Utah (9.1) and Montana (9.6) had the lowest AAIRs in 2019. New Hampshire and Indiana had significant and highest decreases, while Louisiana and Arkansas had significant and largest increases in AAIR. In individual races, TNBC displayed disparities in temporal trends among age groups, regions and disease stages. Surprisingly, Non-Hispanic White and Hispanic TNBC women (0-34 years), and Non-Hispanic Black women (≥70 years) during the entire period, as well as Asian or Pacific Islander women in the South region had increased trends between 2011 and 2017. Conclusion: Our study demonstrates an overall decreased trend of TNBC incidence in the past decade. Its incidence displayed disparities among races, age groups, regions and disease stages. Special attention is needed for a heavy burden in Non-Hispanic Black and increased trends in certain groups.

Hub gene target of glioblastoma: LOX, SERPINH1 and TGFBI.

Glioblastoma (GBM) is a malignant tumor. The long-term prognosis of the patients is poor. Therefore, it is of important clinical value to further explore the pathogenesis and look for molecular markers for early diagnosis and targeted treatment. Two expression profiling datasets [GSE50161 (GPL570 platform), GSE116520 (GPL10558 platform)] were respectively downloaded from the gene expression omnibus database. Volcano diagrams show the Differently expressed genes (DEGs) of GSE50161 and GSE116520. A Venn diagram revealed 467 common DEGs between the 2 datasets. Lysyl oxidase (LOX), serpin family H member 1 (SERPINH1) and transforming growth factor beta induced (TGFBI) were negatively correlated with the overall survival rate in patients with GBM. The hub genes are high in GBM tumor tissues. The relative expression levels of LOX, SERPINH1 and TGFBI were significantly higher in GBM samples, compared with the normal brain tissues groups. Bioinformatics technology could be a useful tool to predict progression of GBM and to explore the mechanism of GBM.LOX, SERPINH1 and TGFBI may be involved in the mechanism of the occurrence and development of GBM, and may be used as molecular targets for early diagnosis and specific treatment. DEGs identified using GEO2R. Functional annotation of DEGs using Kyoto Encyclopedia of Genes and Genomes and gene body pathway enrichment analysis. Construction of a protein-protein interaction network. The pathway and process enrichment analysis of the hub genes were performed by Metascape. Survival analysis was performed in gene expression profiling interactive analysis. Real-time fluorescent quantitative polymerase chain reaction assay was performed to verify. The animal model was established for western blot test analysis.

Hub genes for early diagnosis and therapy of adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a subtype of craniopharyngioma, a neoplastic disease with a benign pathological phenotype but a poor prognosis in the sellar region. The disease has been considered the most common congenital tumor in the skull. Therefore, this article aims to identify hub genes that might serve as genetic markers of diagnosis, treatment, and prognosis of ACP. METHODS: The procedure of this research includes the acquisition of public data, identification and functional annotation of differentially expressed genes (DEGs), construction and analysis of protein-protein interaction network, and the mining and analysis of hub genes by Spearman-rho test, multivariable linear regression, and receiver operator characteristic curve analysis. Quantitative real-time polymerase chain reaction was used to detect the level of mRNA of relative genes. RESULTS: Among 2 datasets, a total of 703 DEGs were identified, mainly enriched in chemical synaptic transmission, cell adhesion, odontogenesis of the dentin-containing tooth, cell junction, extracellular region, extracellular space, structural molecule activity, and structural constituent of cytoskeleton. The protein-protein interaction network was composed of 4379 edges and 589 nodes. Its significant module had 10 hub genes, and SYN1, SYP, and GRIA2 were significantly down-regulated with ACP. CONCLUSION: In a word, we find out the DEGs between ACP patients and standard samples, which are likely to play an essential role in the development of ACP. At the same time, these DEGs are of great value in tumors' diagnosis and targeted therapy and could even be mined as biological molecular targets for diagnosing and treating ACP patients.

Apatinib Induces Ferroptosis of Glioma Cells through Modulation of the VEGFR2/Nrf2 Pathway.

Background: Glioma is a common tumor that originated from the brain, and molecular targeted therapy is one of the important treatment modalities of glioma. Apatinib is a small-molecule tyrosine kinase inhibitor, which is widely used for the treatment of glioma. However, the underlying molecular mechanism has remained elusive. Recently, emerging evidence has proved the remarkable anticancer effects of ferroptosis. In this study, a new ferroptosis-related mechanism of apatinib inhibiting proliferation of glioma cells was investigated, which facilitated further study on inhibitory effects of apatinib on cancer cells. Methods: Human glioma U251 and U87 cell lines and normal astrocytes were treated with apatinib. Ferroptosis, cell cycle, apoptosis, and proliferation were determined. A nude mouse xenograft model was constructed, and tumor growth rate was detected. Tumor tissues were collected to estimate ferroptosis levels and to identify the relevant pathways after treatment with apatinib. Results: Treatment with apatinib could induce loss of cell viability of glioma cells, but not of normal astrocytes, through eliciting ferroptosis in vitro and in vivo. It was also revealed that apatinib triggered ferroptosis of glioma cells via inhibiting the activation of nuclear factor erythroid 2-related factor 2/vascular endothelial growth factor receptor 2 (Nrf2/VEFGR2) pathway. The overexpression of Nrf2 rescued the therapeutic effects of apatinib. Conclusion: Our study proved that treatment with apatinib could restrain proliferation of glioma cells through induction of ferroptosis via inhibiting the activation of VEGFR2/Nrf2/Keap1 pathway. Overexpression of Nrf2 could counteract the induction of ferroptosis by apatinib.

Erratum: Borneol promotes apoptosis of Human Glioma Cells through regulating HIF-1a expression via mTORC1/eIF4E pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.45304.].

Prognosis of Oligodendroglioma Patients Stratified by Age: A SEER Population-Based Analysis.

PURPOSE: Glioma may affect patients of any age. So far, only a limited number of big data studies have been conducted concerning oligodendroglioma (OG) in diverse age groups. This study evaluated the risk factors for OG in different age groups using the Surveillance, Epidemiology, and End Results (SEER) database built by the National Cancer Institute, which is part of the National Institutes of Health. PATIENTS AND METHODS: A total of 5437 cases within the SEER database were included. These patients were divided into seven age groups. The Kaplan-Meier method was employed for survival analysis. The independent risk factors for the survival of OG patients were identified using the Cox regression model. A nomogram was drawn with R software based on the independent risk factors. The X-tile software was adopted to find the optimal age group at diagnosis. RESULTS: The all-cause mortality and the tumor-specific mortality increased with age. The univariate analysis showed that the patients' age, gender, primary lesion location, side affected by the primary lesion (left or right), surgery for the primary lesion, and tumor size were correlated with survival (P<0.05). Multivariate Cox regression analysis showed that age was an independent risk factor for the survival of OG patients (P<0.05). The optimal cutoff value of age in terms of overall survival (OS) and cause-specific survival (CSS) were identified as 48 and 61 years and 48 and 59 years, respectively. CONCLUSION: The older the age, the worse the survival would be. That's, the mortality increased with age. In the clinic, healthcare professionals should be fully aware of the variability in the prognosis of OG patients in different age groups. Therefore, individualized treatments are recommended to OG patients in different age groups to optimize the prognosis.

Role of Borneol Induced Autophagy in Enhancing Radiosensitivity of Malignant Glioma.

Glioma is the common primary craniocerebral malignancy with unfavorable prognosis. It is currently treated by surgical resection supplemented by radiotherapy, although the resistance of glioma cells to radiation limits the therapeutic outcomes. The aim of the present study was to determine the potential radiosensitizing effects of borneol and the underlying mechanisms. We found that borneol administration along with radiotherapy significantly inhibited the growth of primary glioma cells in vitro and in vivo. Furthermore, borneol markedly increased the number of autophagosomes in the glioma cells, which coincided with increased expression of beclin-1 and LC3. And the combination of borneol and radiation exposure significantly decreased the expression levels of HIF-1α, mTORC1 and eIF4E. In addition, silencing mTORC1 and eIF4E upregulated Beclin-1 and LC3 and decreased the expression of HIF-1α, thereby inhibiting tumor cell proliferation. Our findings suggest that borneol sensitizes glioma cells to radiation by inducing autophagy via inhibition of the mTORC1/eIF4E/HIF-1α regulatory axis.

The role m6A RNA methylation is CNS development and glioma pathogenesis.

Epigenetic abnormalities play a crucial role in many tumors, including glioma. RNA methylation occurs as an epigenetic modification similar to DNA methylation and histone modification. m6A methylation is the most common and most intensively studied RNA methylation, which can be found throughout the RNA life cycle and exert biological functions by affecting RNA metabolism. The m6A modification is primarily associated with three types of protease, which are encoded by the writer, eraser and reader genes, respectively. It has been shown that the m6A methylation has close connections with the occurrence and development of many tumors, including glioma. In this study, the concept and the research progress of m6A methylation are reviewed, especially the role of m6A methylation in glioma. Moreover, we will discuss how glioma is paving the way to the development of new therapeutic options based on the inhibition of m6A deposition.

Hub biomarkers for the diagnosis and treatment of glioblastoma based on microarray technology.

BACKGROUND: Glioblastoma (GBM) is the most common clinical intracranial malignancy worldwide, and the most common supratentorial tumor in adults. GBM mainly causes damage to the brain tissue, which can be fatal. This research explored potential gene targets for the diagnosis and treatment of GBM using bioinformatic technology. METHODS: Public data from patients with GBM and controls were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified by Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus 2R (GEO2R). Construction of the protein-protein interaction network and the identification of a significant module were performed. Subsequently, hub genes were identified, and their expression was examined and compared by real-time quantitative (RT-q)PCR between patients with GBM and controls. RESULTS: GSE122498 (GPL570 platform), GSE104291 (GPL570 platform), GSE78703_DMSO (GPL15207 platform), and GSE78703_LXR (GPL15207 platform) datasets were obtained from the GEO. A total of 130 DEGs and 10 hub genes were identified by GEPIA and GEO2R between patients with GBM and controls. Of these, strong connections were identified in correlation analysis between CCNB1, CDC6, KIF23, and KIF20A. RT-qPCR showed that all 4 of these genes were expressed at significantly higher levels in patients with GBM compared with controls. CONCLUSIONS: The hub genes CCNB1, CDC6, KIF23, and KIF20A are potential biomarkers for the diagnosis and treatment of GBM.

Long non-coding RNA TP73-AS1 is a potential immune related prognostic biomarker for glioma.

Glioma is one of the most common primary brain tumors, and is divided into low-grade and high-grade gliomas. Long non-coding RNAs have been increasingly implicated in the pathogenesis and prognosis of glioma. Here, we demonstrated that the long non-coding RNA TP73-AS1 is differentially expressed among gliomas with different clinicopathological features in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and GEO glioma datasets; high expression of TP73-AS1 was associated with poor clinical features, including age, stage, IDH mutation status, 1p/19q co-deletion status and overall survival. Measuring TP73-AS1 expression using real-time PCR showed the same result for 76 glioma tissue samples from our hospital. The infiltration levels of various immune cells in the tumor microenvironment were found to be significantly higher in patients with high expression of TP73-AS1. Taken together, our results suggest that TP73-AS1 has potential as a prognostic glioma biomarker. Moreover, the knowledge that TP73-AS1 affects the glioma immune microenvironment may provide new information for the immunological research and treatment of glioma.

Combined Diagnostic Significance of Preoperative Serum ß2-Microglobulin and Routine Blood Test in Patients with High-grade Glioma and Solitary Brain Metastasis.

BACKGROUND: High-grade glioma (HGG) and solitary brain metastasis (sBM) patients show similar symptoms in clinical practice, and accurately differential diagnosis directly affects the management and prognosis of patients. The aim of this study was to distinguish two entities by preoperative serum ß2-microglobulin (ß2-m) and routine blood test-associated inflammatory indexes including, white blood cell (WBC), neutrophils, lymphocytes, monocytes, and platelets count, red cell distribution width (RDW), platelet distribution width (PDW), neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR). PATIENTS AND METHODS: A retrospective analysis was performed in the Cancer Hospital of the University of Chinese Academy of Sciences from January 2015 to December 2019, including 127 patients of newly pathologically diagnosed with HGG and 174 patients with sBM. Clinical information including age, gender, pathological diagnosis, preoperative serum ß2-m and routine blood tests were collected, and NLR and MLR were calculated. The diagnostic significance of these markers for HGG and sBM was assessed by receiver operating characteristic (ROC) curves. RESULTS: The patients with sBM had significantly higher values of preoperative age, ß2-m, NLR and MLR as well as lower lymphocytes count than patients with HGG. Besides, the area under the curve (AUC) in differentiating HGG from sBM was 0.625 (95%CI: 0.561-0.689) for age, 0.655 (0.594-0.717) for ß2-m, 0.634 (0.571-0.698) for NLR and 0.622 (0.559-0.686) for MLR, and the combination of Age+ß2-m+NLR+MLR showed the best diagnostic performance with AUC of 0.731 (0.675-0.788) and 0.048*Age+0.001*ß2-m+0.201*NLR+0.594*MLR>5.813 could indicate sBM rather than HGG. CONCLUSION: The Age+ß2-m+NLR+MLR combination was revealed as an inexpensive and noninvasive biomarker for differentiating between HGG and sBM before surgery.

Borneol promotes apoptosis of Human Glioma Cells through regulating HIF-1a expression via mTORC1/eIF4E pathway.

The main reason for the failure of malignant glioma treatment is local tumor recurrence. Tumor cells in hypoxic microenvironment activate HIF-1 α transcription, and thus promoting tumor invasion and metastasis is one of the important reasons. In our previous study, we clearly established that borneol opens the blood-brain tumor barrier and its related mechanism. However, the effects of borneol itself on glioma proliferation have not yet been elucidated. Therefore, in this study, we evaluated the effect of borneol on glioma by constructing in vivo SD rat brain glioma model and in vitro human primary cultured glioma cell model. We found that borneol could suppress the proliferation of primary glioma cells and the tumor volume of SD rat brain glioma. Further, we measured the apoptosis effect induced by borneol in human primary cultured glioma cells. The results showed that the higher the concentration of borneol, the higher the apoptosis rate of human primary cultured glioma cells, but the effect was reversed after transfection of HIF-1 overexpression plasmid; In addition, borneol could downregulate the expression of Bcl-2 and upregulation the expression of Bax and caspase-3, similarly, the effect was also reversed after transfection of HIF-1 overexpression plasmid, suggesting that the apoptosis effect induced by borneol in human primary cultured glioma cells is mediated via HIF-1α. Moreover, the bioinformatics analysis of correlation between HIF-1α and apoptosis-related factors based on CGGA database showed that there was a positive correlation between the expression of eIF4E and HIF-1 α (P < 0.05), and in patients with high expression of eIF4E and HIF-1α had poor survival and prognosis (P<0.001). It was further discovered that in the human primary cultured glioma cells borneol regulated HIF-1a expression via mTORC1/eIF4E pathway. In conclusion, the findings of the present study suggest that HIF-1α may be a key factor in borneol induced apoptosis of glioma cells, and mTORC1 / eIF4E pathway is involved in the HIF-1α regulation by borneol in malignant glioma. Our results not only reveal the target and molecular mechanism and action of borneol leading to promote apoptosis in glioma cells, but also provide experimental basis and theoretical support for the clinical application of borneol.

Diagnostic values of thyroglobulin in lymph node fine-needle aspiration washout: a systematic review and meta-analysis diagnostic values of FNA-Tg.

Thyroglobulin measurement in the needle washout after fine-needle aspiration (FNA-Tg) served as an important measurement for suspicious recurrent or metastatic lesions. We conducted a pooled analysis to evaluate the diagnostic accuracy of FNA-Tg and searched electronic databases for original articles in English from 1993 through 2017. Finally, a total of 22 studies containing 2,670 lymph nodes (LNs) that enrolled participants with suspicious neck LNs during thyroid nodule workup or papillary thyroid cancer (PTC) follow-up were included. In our analysis, the overall pooled sensitivity for FNA-Tg was 0.91 (95%CI: 0.87-0.93), specificity was 0.94 (95% CI: 0.91-0.96). Meta regression revealed that the cutoff value and status of serum Tg were sources of heterogeneity for sensitivity, and the cutoff value was source of heterogeneity for specificity. Additionally, the cutoff value and status of serum Tg were sources of heterogeneity in the joint model. Subgroup analysis about cut-off value showed that the choice of 1 ng/mL had highest sensitivity, 40 ng/mL had highest specificity. At last, we arrived at the conclusion that FNA-Tg measurement had high specificity and sensitivity in the early detection of LNs metastases from PTC by our meta-analysis. The technique was simple and could be recommended to apply in any FNA facility, especially when LN were small-sized. Significantly, a better standardization of criteria for FNA-Tg detection and cutoff value was required to provide useful data and to improve management of PTC patients in the future.

MST1 suppresses viability and promotes apoptosis of glioma cells via upregulating SIRT6 expression.

It has been well established that mammalian sterile 20-like 1 (MST1) functions as a suppressor via regulating cell progression in many tumors. However, the molecular mechanism of MST1 on regulating glioma progression remains unclear. Here, we discovered that MST1 was robustly down-regulated in glioma tissues and cells. Functional analysis showed that over-expression of MST1 downregulated viability and colony formation and promoted apoptosis of glioma cells. Our results also identified that MST1 positively regulated expression of SIRT6 (Sirtuin 6) via transcriptional factor FOXO3a (Forkhead box O3a). Furthermore, the functional role of MST1 in glioma cell viability (or apoptosis) were significantly reversed after knocking down of SIRT6. Our research indicates that MST1 is a potential biomarker for the prognosis and diagnosis of glioma and provides new direction on the molecular mechanism of glioma progression and development.

FER1L4/miR-372/E2F1 works as a ceRNA system to regulate the proliferation and cell cycle of glioma cells.

Long non-coding RNAs have recently become a key regulatory factor for cancers, whereas FER1L4, a newly discovered long non-coding RNA, has been mostly studied in gastric carcinoma and colon cancer cases. The functions and molecular mechanism of FER1L4 have been rarely reported in glioma malignant phenotypes. In this study, it was found that the expression of LncRNA FER1L4 is upregulated in high-grade gliomas than in low-grade cases and that a high expression of LncRNA FER1L4 predicts poor prognosis of gliomas. Meanwhile, in vitro study suggests that expression of FER1L4 with SiRNA knockdown obviously suppresses cell cycle and proliferation. It is further demonstrated by experiments that the FER1L4 knockdown suppresses growth of in vivo glioma. Besides, it is found in our study that LncRNA FER1L4 expression is positively correlated with E2F1 mRNA expression. After knockdown of FER1L4 expression, E2F1 expression is significantly down-regulated, whereas the expression of miR-372 is significantly up-regulated; the up-regulation of miR-372 leads to significant down-regulation of FER1L4 and E2F1 expression. In addition, it is also found that FER1L4 can be used as competitive endogenous RNA to interact or bind with miR-371 and thereby up-regulate E2F1, thus promoting the cycle and proliferation of glioma cells. It may be one of the molecular mechanisms in which FER1L4 plays its oncogene-like role in gliomas.