Oxidative stress genes define two subtypes of triple-negative breast cancer with prognostic and therapeutic implications.

Introduction: Oxidative stress (OS)-related genes have been confirmed to be closely related to the prognosis of triple-negative breast cancer (TNBC) patients; despite this fact, there is still a lack of TNBC subtype strategies based on this gene guidance. Here, we aimed to explore OS-related subtypes and their prognostic value in TNBC. Methods: Data from The Cancer Genome Atlas (TCGA)-TNBC and Sequence Read Archive (SRA) (SRR8518252) databases were collected, removing batch effects using a combat method before analysis. Consensus clustering analysis identified two OS subtypes (clusters A and B), with cluster A showing a better prognosis. Immune infiltration characteristics were analyzed using ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) algorithms, revealing higher ImmuneScore and ESTIMATEscore in cluster A. Tumor-suppressive immune cells, human leukocyte antigen (HLA) genes, and three immune inhibitors were more prevalent in cluster A. Results: An eight-gene signature, derived from differentially expressed genes, was developed and validated as an independent risk factor for TNBC. A nomogram combining the risk score and clinical variables accurately predicted patient outcomes. Finally, we also validated the classification effect of subtypes using hub markers of each subtype in the test dataset. Conclusion: Our study reveals distinct molecular clusters based on OS-related genes to better clarify the reactive oxygen species (ROS)-mediated progression and the crosstalk between the ROS and tumor microenvironment (TME) in this heterogenetic disease, and construct a risk prognostic model which could provide more support for clinical treatment decisions.

Sensory Ion Channel Candidates Inform on the Clinical Course of Pancreatic Cancer and Present Potential Targets for Repurposing of FDA-Approved Agents.

Background: Transient receptor potential channels (TRPs) have been demonstrated to take on functions in pancreatic adenocarcinoma (PAAD) biology. However, little data are available that validate the potential of TRP in a clinical translational setting. Methods: A TRPs-related gene signature was constructed based on the Cox regression using a TCGA-PAAD cohort and receiver operating characteristic (ROC) was used to evaluate the predictive ability of this model. Core genes of the signature were screened by a protein-to-protein interaction (PPI) network, and expression validated by two independent datasets. The mutation analysis and gene set enrichment analysis (GSEA) were conducted. Virtual interventions screening was performed to discover substance candidates for the identified target genes. Results: A four TRPs-related gene signature, which contained MCOLN1, PKD1, TRPC3, and TRPC7, was developed and the area under the curve (AUC) was 0.758. Kaplan−Meier analysis revealed that patients with elevated signature score classify as a high-risk group featuring significantly shorter recurrence free survival (RFS) time, compared to the low-risk patients (p < 0.001). The gene prediction model also had a good predictive capability for predicting shortened overall survival (OS) and disease-specific survival (DSS) (AUC = 0.680 and AUC = 0.739, respectively). GSEA enrichment revealed the core genes of the signature, TRPC3 and TRPC7, were involved in several cancer-related pathways. TRPC3 mRNA is elevated in cancer tissue compared to control tissue and augmented in tumors with lymph node invasion compared to tumors without signs of lymph node invasion. Virtual substance screening of FDA approved compounds indicates that four small molecular compounds might be potentially selective not only for TRPC3 protein but also as a potential binding partner to TRPC7 protein. Conclusions: Our computational pipeline constructed a four TRP-related gene signature that enables us to predict clinical prognostic value of hitherto unrecognized biomarkers for PAAD. Sensory ion channels TRPC3 and TRPC7 could be the potential therapeutic targets in pancreatic cancer and TRPC3 might be involved in dysregulating mitochondrial functions during PAAD genesis.

Naloxone for severe traumatic brain injury: a meta-analysis.

OBJECTIVE: The efficiency of naloxone for the management of secondary brain injury after severe traumatic brain injury (sTBI) remains undefined. The aim of this study is to evaluate the current evidence regarding the clinical efficiency and safety of naloxone as a treatment for sTBI in mainland China. METHODOLOGY/PRINCIPAL FINDINGS: A systematic search of the China Biology Medicine disc (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Internet (CNKI), and Wan Fang Database was performed to identify randomized controlled trials (RCTs) of naloxone treatment for patients with sTBI in mainland China. The quality of the included trials was assessed, and the RevMan 5.1 software was employed to conduct this meta-analysis. Nineteen RCTs including 2332 patients were included in this study. The odds ratio (OR) showed statistically significant differences between the naloxone group and the control group (placebo) in terms of mortality at 18 months after treatment (OR, 0.51, 95%CI: 0.38-0.67; p<0.00001), prevalence of abnormal heart rates (OR, 0.30, 95%CI: 0.21-0.43; p<0.00001), abnormal breathing rate (OR, 0.25, 95%CI: 0.17-0.36; p<0.00001) at discharge, the level of intracranial pressure at discharge (OR, 2.00, 95%CI: 1.41-2.83; p = 0.0001), verbal or physical dysfunction rate (OR, 0.65, 95%CI: 0.43-0.98; p = 0.04), and severe disability rate (OR, 0.47, 95%CI: 0.30-0.73; p = 0.0001) at 18 months after the treatment. The mean difference (MD) showed statistically significant differences in awakening time at discharge (MD, -4.81, 95%CI: -5.49 to -4.12; p<0.00001), and GCS at 3 days (MD, 1.00, 95%CI: 0.70-1.30; p<0.00001) and 10 days (MD, 1.76, 95%CI: 1.55-1.97; p<0.00001) after treatment comparing naloxone with placebo group. CONCLUSIONS/SIGNIFICANCE: This study indicated that applying naloxone in the early stage for sTBI patients might effectively reduce mortality, control intracranial pressure (ICP), and significantly improve the prognosis.

Characterization of pituitary tumor transforming gene in meningiomas.

BACKGROUND: Pituitary tumor transforming gene (PTTG) is an oncogene and has been detected in several tumors of unrelated histological origin. However, its role in meningiomas is unknown so far. We aim to investigate PTTG expression in intracranial meningiomas, and clarify the relationship between PTTG and the histopathological types of tumors. MATERIALS AND METHODS: Over a 7-year period, 195 meningioma specimens were collected from 195 patients. Seventeen nonneoplastic meningeal tissues were used as controls. We analyze PTTG expression by tissue microarray with immunohistochemistry. RESULTS: Immunoexpression of PTTG was identified in 172 of 195 meningiomas, accounting for 88.2%. All of immunoexpression of tumors were found to be cytoplasmic, and no nuclear expression was observed. In the control group, there were 3 of 17 specimens (17.6%) with positive PTTG expression. The percentage of high expression WHO subtypes of meningiomas ranged from 0% to 95.7%. We further stratified the tumors into 3 subgroups based on pathological grading (WHO grade I, WHO grade II and III, control), and there was significant intergroup difference in PTTG expression (p<0.001). CONCLUSION: This study demonstrated that PTTG was expressed in most of meningioma tissues, and the degree of PTTG immunostaining was variable in the subtypes of tumors. Further investigations into PTTG expression are required to broaden the pathogenesis research of meningiomas.

Neuroendoscopic surgery versus external ventricular drainage alone or with intraventricular fibrinolysis for intraventricular hemorrhage secondary to spontaneous supratentorial hemorrhage: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Although neuroendoscopy (NE) has been applied to many cerebral diseases, the effect of NE for intraventricular hemorrhage (IVH) secondary to spontaneous supratentorial hemorrhage remains controversial. The purpose of this study was to analyze the effect of NE compared with external ventricular drainage (EVD) alone or with intraventricular fibrinolysis (IVF) on the management of IVH secondary to spontaneous supratentorial hemorrhage. METHODOLOGY/ PRINCIPAL FINDINGS: A systematic search of electronic databases (PubMed, EMBASE, OVID, Web of Science, The Cochrane Library, CBM, VIP, CNKI, and Wan Fang database) was performed to identify related studies published from 1970 to 2013. Randomized controlled trials (RCTs) or observational studies (OS) comparing NE with EVD alone or with IVF for the treatment of IVH were included. The quality of the included trials was assessed by Jaded scale and the Newcastle-Ottawa Scale (NOS). RevMan 5.1 software was used to conduct the meta-analysis. RESULTS: Eleven trials (5 RCTs and 6 ORs) involving 680 patients were included. The odds ratio (OR) showed a statistically significant difference between the NE + EVD and EVD + IVF groups in terms of mortality (OR, 0.31; 95% CI, 0.16-0.59; P=0.0004), effective hematoma evacuation rate (OR, 25.50, 95%CI; 14.30, 45.45; P<0.00001), good functional outcome (GFO) (OR, 4.51; (95%CI, 2.81-7.72; P<0.00001), and the ventriculo-peritoneal (VP) shunt dependence rate (OR, 0.16; 95%CI; 0.06, 0.40; P<0.0001). CONCLUSION: Applying neuroendoscopic approach with EVD may be a better management for IVH secondary to spontaneous supratentorial hemorrhage than NE + IVF. However, there is still no conclusive evidence regarding the preference of NE vs. EVD alone in the case of IVH, because insufficient data has been published thus far. This study suggests that the NE approach with EVD could become an alternative to EVD + IVF for IVH in the future.