Compare the safety and efficacy of endoscopic third ventriculostomy and ventriculoperitoneal shunt placement in infants and children with hydrocephalus: a systematic review and meta-analysis

Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt placement are two surgical options used for treatment of non-communicating hydrocephalus. The purpose of this study was to compare the efficiency and safety of these techniques in pediatric patients. An extensive literature review regarding the clinical outcome, safety and efficiency of ETV and shunting in treatment of hydrocephalus was conducted in Medline, PubMed, Cochrane and Google Scholar databases up to 27 November 2015. Patient demographics, ETV and shunting success and failure rates were extracted. A total of seven two-arm studies were included for quantitative analysis and 25 single-arm studies were included for systematic review. The two-arm studies recruited a total of 6995 patients: 1046 in the ETV group and 5949 in the shunt group. The pooled results showed that the 1 year success rate of ETV and shunt-placement procedure were similar (pooled RR = 0.870, 95% CI = 0.680–1.112, P = 0.266). The failure rate in the ETV treatment group was 0.9 times higher than in the shunt group; however, the results did not reach statistical significance (pooled RR = 0.893, 95% CI = 0.576–1.383, P = 0.611). Both ETV and shunts are associated with similar 1 year success and failure rates. Therefore, there are no current indications to recommend one mode of treatment over the other. Future studies designed to assess the effectiveness of ETV and shunt procedures depending on patient’s age and etiology are warranted.</p

Table_3_Quantitative Ubiquitinomics Revealed Abnormal Ubiquitinated ATP7A Involved in Down-Regulation of ACTH in Silent Corticotroph Adenomas.xls

Ubiquitination is reported to be a critical biological event on ACTH secretion in corticotroph adenomas. However, the effect of ubiquitylation on ACTH secretion in silent corticotroph adenomas (SCAs) remains unclear. The aim of our study was to explore the mechanism of decreased secretion of ACTH in SCAs with ubiquitinomics. The differently expressed ubiquitinated proteins between SCAs and functioning corticotroph adenomas (FCAs) were identified by 4D label-free mass spectrometer, followed by bioinformatics analysis. The function of the candidate ubiquitinated protein ATP7A (K333) was validated in AtT20 cells. A total of 111 ubiquitinated sites corresponding to 94 ubiquitinated proteins were typically different between SCAs and FCAs. Among all the ubiquitinated sites, 102 showed decreased ubiquitination in SCAs, which mapped to 85 ubiquitinated proteins. Pathway enrichment analysis revealed that ubiquitinated proteins were mainly enriched in vesicle pathway and protein secretion pathway. ATP7A (K333) was one of the proteins enriched in vesicle pathway and protein secretion pathway with decreased ubiquitination level in SCAs. In vitro assay indicated that both ATP7A siRNA and omeprazole (ATP7A protein inhibitor) increased the secretion of ACTH in AtT20 cell supernatant compared to control groups (p<0.05). These results indicated that ATP7A might be related to the abnormal expression of ACTH in SCAs and potential for the treatment of SCAs.</p

Table_2_Quantitative Ubiquitinomics Revealed Abnormal Ubiquitinated ATP7A Involved in Down-Regulation of ACTH in Silent Corticotroph Adenomas.xls

Ubiquitination is reported to be a critical biological event on ACTH secretion in corticotroph adenomas. However, the effect of ubiquitylation on ACTH secretion in silent corticotroph adenomas (SCAs) remains unclear. The aim of our study was to explore the mechanism of decreased secretion of ACTH in SCAs with ubiquitinomics. The differently expressed ubiquitinated proteins between SCAs and functioning corticotroph adenomas (FCAs) were identified by 4D label-free mass spectrometer, followed by bioinformatics analysis. The function of the candidate ubiquitinated protein ATP7A (K333) was validated in AtT20 cells. A total of 111 ubiquitinated sites corresponding to 94 ubiquitinated proteins were typically different between SCAs and FCAs. Among all the ubiquitinated sites, 102 showed decreased ubiquitination in SCAs, which mapped to 85 ubiquitinated proteins. Pathway enrichment analysis revealed that ubiquitinated proteins were mainly enriched in vesicle pathway and protein secretion pathway. ATP7A (K333) was one of the proteins enriched in vesicle pathway and protein secretion pathway with decreased ubiquitination level in SCAs. In vitro assay indicated that both ATP7A siRNA and omeprazole (ATP7A protein inhibitor) increased the secretion of ACTH in AtT20 cell supernatant compared to control groups (p<0.05). These results indicated that ATP7A might be related to the abnormal expression of ACTH in SCAs and potential for the treatment of SCAs.</p

Table_2_Identification of biomarkers associated with the invasion of nonfunctional pituitary neuroendocrine tumors based on the immune microenvironment.xlsx

IntroductionThe invasive behavior of nonfunctioning pituitary neuroendocrine tumors (NF-PitNEts) affects complete resection and indicates a poor prognosis. Cancer immunotherapy has been experimentally used for the treatment of many tumors, including pituitary tumors. The current study aimed to screen the key immune-related genes in NF-PitNEts with invasion.MethodsWe used two cohorts to explore novel biomarkers in NF-PitNEts. The immune infiltration-associated differentially expressed genes (DEGs) were obtained based on high/low immune scores, which were calculated through the ESTIMATE algorithm. The abundance of immune cells was predicted using the ImmuCellAI database. WGCNA was used to construct a coexpression network of immune cell-related genes. Random forest analysis was used to select the candidate genes associated with invasion. The expression of key genes was verified in external validation set using quantitative real-time polymerase chain reaction (qRT‒PCR).ResultsThe immune and invasion related DEGs was obtained based on the first dataset of NF-PitNEts (n=112). The immune cell-associated modules in NF-PitNEts were calculate by WGCNA. Random forest analysis was performed on 81 common genes intersected by immune-related genes, invasion-related genes, and module genes. Then, 20 of these genes with the highest RF score were selected to construct the invasion and immune-associated classification model. We found that this model had high prediction accuracy for tumor invasion, which had the largest area under the receiver operating characteristic curve (AUC) value in the training dataset from the first dataset (n=78), the self-test dataset from the first dataset (n=34), and the independent test dataset (n=73) (AUC=0.732/0.653/0.619). Functional enrichment analysis revealed that 8 out of the 20 genes were enriched in multiple signaling pathways. Subsequently, the 8-gene (BMP6, CIB2, FABP5, HOMER2, MAML3, NIN, PRKG2 and SIDT2) classification model was constructed and showed good efficiency in the first dataset (AUC=0.671). In addition, the expression levels of these 8 genes were verified by qRT‒PCR.ConclusionWe identified eight key genes associated with invasion and immunity in NF-PitNEts that may play a fundamental role in invasive progression and may provide novel potential immunotherapy targets for NF-PitNEts.</p

Table_1_Quantitative Ubiquitinomics Revealed Abnormal Ubiquitinated ATP7A Involved in Down-Regulation of ACTH in Silent Corticotroph Adenomas.xls

Ubiquitination is reported to be a critical biological event on ACTH secretion in corticotroph adenomas. However, the effect of ubiquitylation on ACTH secretion in silent corticotroph adenomas (SCAs) remains unclear. The aim of our study was to explore the mechanism of decreased secretion of ACTH in SCAs with ubiquitinomics. The differently expressed ubiquitinated proteins between SCAs and functioning corticotroph adenomas (FCAs) were identified by 4D label-free mass spectrometer, followed by bioinformatics analysis. The function of the candidate ubiquitinated protein ATP7A (K333) was validated in AtT20 cells. A total of 111 ubiquitinated sites corresponding to 94 ubiquitinated proteins were typically different between SCAs and FCAs. Among all the ubiquitinated sites, 102 showed decreased ubiquitination in SCAs, which mapped to 85 ubiquitinated proteins. Pathway enrichment analysis revealed that ubiquitinated proteins were mainly enriched in vesicle pathway and protein secretion pathway. ATP7A (K333) was one of the proteins enriched in vesicle pathway and protein secretion pathway with decreased ubiquitination level in SCAs. In vitro assay indicated that both ATP7A siRNA and omeprazole (ATP7A protein inhibitor) increased the secretion of ACTH in AtT20 cell supernatant compared to control groups (p<0.05). These results indicated that ATP7A might be related to the abnormal expression of ACTH in SCAs and potential for the treatment of SCAs.</p

Table_4_Quantitative Ubiquitinomics Revealed Abnormal Ubiquitinated ATP7A Involved in Down-Regulation of ACTH in Silent Corticotroph Adenomas.xls

Ubiquitination is reported to be a critical biological event on ACTH secretion in corticotroph adenomas. However, the effect of ubiquitylation on ACTH secretion in silent corticotroph adenomas (SCAs) remains unclear. The aim of our study was to explore the mechanism of decreased secretion of ACTH in SCAs with ubiquitinomics. The differently expressed ubiquitinated proteins between SCAs and functioning corticotroph adenomas (FCAs) were identified by 4D label-free mass spectrometer, followed by bioinformatics analysis. The function of the candidate ubiquitinated protein ATP7A (K333) was validated in AtT20 cells. A total of 111 ubiquitinated sites corresponding to 94 ubiquitinated proteins were typically different between SCAs and FCAs. Among all the ubiquitinated sites, 102 showed decreased ubiquitination in SCAs, which mapped to 85 ubiquitinated proteins. Pathway enrichment analysis revealed that ubiquitinated proteins were mainly enriched in vesicle pathway and protein secretion pathway. ATP7A (K333) was one of the proteins enriched in vesicle pathway and protein secretion pathway with decreased ubiquitination level in SCAs. In vitro assay indicated that both ATP7A siRNA and omeprazole (ATP7A protein inhibitor) increased the secretion of ACTH in AtT20 cell supernatant compared to control groups (p<0.05). These results indicated that ATP7A might be related to the abnormal expression of ACTH in SCAs and potential for the treatment of SCAs.</p

Table_5_Quantitative Ubiquitinomics Revealed Abnormal Ubiquitinated ATP7A Involved in Down-Regulation of ACTH in Silent Corticotroph Adenomas.xls

Ubiquitination is reported to be a critical biological event on ACTH secretion in corticotroph adenomas. However, the effect of ubiquitylation on ACTH secretion in silent corticotroph adenomas (SCAs) remains unclear. The aim of our study was to explore the mechanism of decreased secretion of ACTH in SCAs with ubiquitinomics. The differently expressed ubiquitinated proteins between SCAs and functioning corticotroph adenomas (FCAs) were identified by 4D label-free mass spectrometer, followed by bioinformatics analysis. The function of the candidate ubiquitinated protein ATP7A (K333) was validated in AtT20 cells. A total of 111 ubiquitinated sites corresponding to 94 ubiquitinated proteins were typically different between SCAs and FCAs. Among all the ubiquitinated sites, 102 showed decreased ubiquitination in SCAs, which mapped to 85 ubiquitinated proteins. Pathway enrichment analysis revealed that ubiquitinated proteins were mainly enriched in vesicle pathway and protein secretion pathway. ATP7A (K333) was one of the proteins enriched in vesicle pathway and protein secretion pathway with decreased ubiquitination level in SCAs. In vitro assay indicated that both ATP7A siRNA and omeprazole (ATP7A protein inhibitor) increased the secretion of ACTH in AtT20 cell supernatant compared to control groups (p<0.05). These results indicated that ATP7A might be related to the abnormal expression of ACTH in SCAs and potential for the treatment of SCAs.</p

Image_1_High systemic inflammation score is associated with adverse survival in skull base chordoma.tif

BackgroundThe systemic inflammation score (SIS), based on preoperative lymphocyte to monocyte ratio (LMR) and albumin (ALB), was recently developed and is demonstrated to be a novel prognostic indicator in several cancers. However, data discussing the utility of SIS in chordoma are lacking. We aimed to investigate the distribution and the prognostic role of SIS in primary skull base chordoma patients undergoing surgery.Material and methodsPreoperative SIS was retrospectively collected from 183 skull base chordoma patients between 2008 and 2014 in a single center. Its associations with clinical features and overall survival (OS) were further analyzed. The SIS-based nomogram was developed and evaluated by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).ResultsThe numbers of patients in the SIS 2, 1, and 0 group were 29 (15.8%), 60 (32.8%), 94 (51.4%), respectively. High SIS was associated with older age (p = 0.008), brainstem involvement of tumors (p = 0.039), and adverse OS (p ConclusionsThe SIS is a promising, simple prognostic biomarker, and the SIS-based nomogram serves as a potential risk stratification tool for outcome in skull base chordoma patients.</p

DataSheet_1_Proteomics Analysis Identified ASNS as a Novel Biomarker for Predicting Recurrence of Skull Base Chordoma.docx

BackgroundThe prognostic factors of skull base chordoma associated with outcomes of patients after surgery remain inadequately identified. This study was designed to identify a novel prognostic factor for patients with skull base chordoma.MethodUsing a proteomic technique, the tumor biomarkers that were upregulated in the rapid-recurrence group of chordoma were screened and then narrowed down by bioinformatic analysis. Finally one potential biomarker was chosen for validation by immunohistochemistry using tissue microarray (TMA). A total of 187 patients included in TMA were randomly divided into two cohorts, the training cohort included 93 patients and the validation cohort included 94 patients. Kaplan-Meier survival analysis was used to assess the patients’ survival. Univariable and multivariable Cox regression analysis were used to identify prognostic factors predicting recurrence-free survival (RFS). CCK-8 assay, clonal formation assay and transwell assay were used to test the effect of asparagine synthetase (ASNS) on the proliferation, migration and invasion in chordoma cell lines.ResultsAmong 146 upregulated proteins, ASNS was chosen as a potential prognostic biomarker after bioinformatics analysis. The H-scores of ASNS ranged from 106.27 to 239.58 in TMA. High expression of ASNS was correlated with shorter RFS in both the training cohort (p = 0.0093) and validation cohort (p ConclusionThis study indicates that high expression of ASNS is correlated with poor prognosis of patients with skull base chordoma. ASNS may be a useful prognostic factor for patients with skull base chordoma.</p

DataSheet_2_Proteomics Analysis Identified ASNS as a Novel Biomarker for Predicting Recurrence of Skull Base Chordoma.xlsx

BackgroundThe prognostic factors of skull base chordoma associated with outcomes of patients after surgery remain inadequately identified. This study was designed to identify a novel prognostic factor for patients with skull base chordoma.MethodUsing a proteomic technique, the tumor biomarkers that were upregulated in the rapid-recurrence group of chordoma were screened and then narrowed down by bioinformatic analysis. Finally one potential biomarker was chosen for validation by immunohistochemistry using tissue microarray (TMA). A total of 187 patients included in TMA were randomly divided into two cohorts, the training cohort included 93 patients and the validation cohort included 94 patients. Kaplan-Meier survival analysis was used to assess the patients’ survival. Univariable and multivariable Cox regression analysis were used to identify prognostic factors predicting recurrence-free survival (RFS). CCK-8 assay, clonal formation assay and transwell assay were used to test the effect of asparagine synthetase (ASNS) on the proliferation, migration and invasion in chordoma cell lines.ResultsAmong 146 upregulated proteins, ASNS was chosen as a potential prognostic biomarker after bioinformatics analysis. The H-scores of ASNS ranged from 106.27 to 239.58 in TMA. High expression of ASNS was correlated with shorter RFS in both the training cohort (p = 0.0093) and validation cohort (p ConclusionThis study indicates that high expression of ASNS is correlated with poor prognosis of patients with skull base chordoma. ASNS may be a useful prognostic factor for patients with skull base chordoma.</p