Use of Genome-Scale Integrated Analysis to Identify Key Genes and Potential Molecular Mechanisms in Recurrence of Lower-Grade Brain Glioma.

BACKGROUND The aim of this study was to identify gene signals for lower-grade glioma (LGG) and to assess their potential as recurrence biomarkers. MATERIAL AND METHODS An LGG-related mRNA sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA) Informix. Multiple bioinformatics analysis methods were used to identify key genes and potential molecular mechanisms in recurrence of LGG. RESULTS A total of 326 differentially-expressed genes (DEGs), were identified from 511 primary LGG tumor and 18 recurrent samples. Gene ontology (GO) analysis revealed that the DEGs were implicated in cell differentiation, neuron differentiation, negative regulation of neuron differentiation, and cell proliferation in the forebrain. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database suggests that DEGs are associated with proteoglycans in cancer, the Wnt signaling pathway, ECM-receptor interaction, the PI3K-Akt signaling pathway, transcriptional deregulation in cancer, and the Hippo signaling pathway. The hub DEGs in the protein-protein interaction network are apolipoprotein A2 (APOA2), collagen type III alpha 1 chain (COL3A1), collagen type I alpha 1 chain (COL1A1), tyrosinase (TYR), collagen type I alpha 2 chain (COL1A2), neurotensin (NTS), collagen type V alpha 1 chain (COL5A1), poly(A) polymerase beta (PAPOLB), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and anomalous homeobox (ANHX). GSEA revealed that the following biological processes may associated with LGG recurrence: cell cycle, DNA replication and repair, regulation of apoptosis, neuronal differentiation, and Wnt signaling pathway. CONCLUSIONS Our study demonstrated that hub DEGs may assist in the molecular understanding of LGG recurrence. These findings still need further molecular studies to identify the assignment of DEGs in LGG.

Establishment and Validation of a Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Lower-Grade Glioma.

Background: The prognosis of lower-grade glioma (LGG) is highly variable, and more accurate predictors are still needed. The aim of our study was to explore the prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in LGG and to develop a novel risk signature for predicting survival with LGG. Methods: We first integrated multiple datasets to screen for prognostic ferroptosis-related lncRNAs in LGG. A least absolute shrinkage and selection operator (LASSO) analysis was then utilized to develop a risk signature for prognostic prediction. Based on the results of multivariate Cox analysis, a prognostic nomogram model for LGG was constructed. Finally, functional enrichment analysis, single-sample gene set enrichment analysis (ssGSEA), immunity, and m6A correlation analyses were conducted to explore the possible mechanisms by which these ferroptosis-related lncRNAs affect survival with LGG. Results: A total of 11 ferroptosis-related lncRNAs related to the prognosis of LGG were identified. Based on prognostic lncRNAs, a risk signature consisting of 8 lncRNAs was constructed and demonstrated good predictive performance in both the training and validation cohorts. Correlation analysis suggested that the risk signature was closely linked to clinical features. The nomogram model we constructed by combining the risk signature and clinical parameters proved to be more accurate in predicting the prognosis of LGG. In addition, there were differences in the levels of immune cell infiltration, immune-related functions, immune checkpoints, and m6A-related gene expression between the high- and low-risk groups. Conclusion: In summary, our ferroptosis-related lncRNA signature exhibits good performance in predicting the prognosis of LGG. This study may provide useful insight into the treatment of LGG.

Surgical Management and Functional Outcomes of Cavernous Malformations Involving the Medulla Oblongata.

OBJECTIVE: The aim of this study was to evaluate the clinical features, surgical complications, and functional outcomes of the surgical treatment of patients with cavernous malformations (CMs) involving the medulla oblongata. METHODS: The charts of 69 patients undergoing surgical treatment of CMs in the medulla oblongata, pontomedullary, and cervicomedullary junctions between 2011 and 2017 were retrospectively reviewed. Patient demographics, lesion characteristics, operative documents, and patient outcomes were examined. RESULTS: Of the 69 patients, the male-to-female ratio was 1.3. The mean patient age was 32.6 years, and the mean mRS score was 2.7 on admission. Postoperatively, 21 patients (30.4%) had deficits of cough reflexes, and 6 patients (8.7%) experienced respiratory rhythm disorder and dyspnea. The mean follow-up duration was 35.3 months. At the last follow-up evaluation, the mean mRS score was 1.8, and 53 patients (80.3%) had favorable outcomes, with mRS scores ≤2. The conditions of the patients improved in 45 cases (68.2%), remained unchanged in 11 cases (16.7%), and worsened in 10 cases (15.1%) relative to their preoperative baseline. The independent adverse factors for long-term functional outcome were increased age, multiple hemorrhages, presence of developmental venous anomalies, and lack of perilesional edema. CONCLUSIONS: Respiratory dysfunction and deficits of cough reflexes can commonly occur during the early postoperative period for surgical resection of CMs involving the medulla oblongata. Favorable functional outcomes can be achieved by surgery, especially for younger patients who experience fewer hemorrhages and have lesions with perilesional edema and the absence of developmental venous anomalies.

Surgical Management and Risk Factors of Postoperative Respiratory Dysfunction of Cavernous Malformations Involving the Medulla Oblongata.

OBJECTIVE: To evaluate surgical management of cavernous malformations (CMs) involving the medulla oblongata and to predict risk factors of postoperative respiratory dysfunction (RDF). METHODS: Patient data from individuals who underwent surgical treatment for CMs involving the medulla oblongata were retrospectively reviewed. Patients with postoperative RDF and/or deficits of the cough reflex (CR, ≥7 days) were deemed as having bad respiratory statuses. A binary logistic regression analysis tested the association of preoperative predictors with bad postoperative respiratory status. RESULTS: The study consisted of 69 patients. Preoperatively, 9 patients (13.0%) had dyspnea, and 4 (5.8%) had hypoxemia. Postoperatively, 11 patients (15.9%) had bad respiratory statuses, including RDF as a respiratory rhythm disorder and/or dyspnea in 6 patients, and ≥7 days of CR deficits in 5 patients. With a mean follow-up duration of 35.3 months, the neurologic status improved in 45 patients (68.2%), remained unchanged in 11 (16.7%), and worsened in 10 (15.1%) relative to the preoperative baseline. A multivariate logistic regression analysis identified that the independent adverse factors of bad postoperative respiratory status were multiple preoperative hemorrhages, large lesion size, and surgical intervention during the chronic period (>8 weeks). CONCLUSIONS: Postoperative RDF and CR deficits could commonly occur in patients with CMs involving the medulla oblongata. However, patients with fewer preoperative hemorrhages, small lesion size, and operation within 8 weeks of the last bleeding are prone to be associated with a reduced possibility of bad postoperative respiratory status.

Surgical Treatment of the Medullary Cavernous Malformations: 53 Cases.

OBJECTIVE: The aim of this study was to investigate patient clinical features, surgical complications and outcomes, and the prognostic risk factors of surgical treatment of cavernous malformations (CMs) involving the medulla oblongata. METHODS: The charts of 53 patients who underwent surgical treatment for CMs involving the medulla oblongata between 2011 and 2017 were reviewed retrospectively. Patient demographics, lesion characteristics, operative documents, and patient outcomes were examined. RESULTS: The study population consisted of 53 patients, with a male/female ratio of 1.4 and a mean age of 32.6 years. Eighteen patients (34.0%) had respiratory dysfunction, and 2 patients (3.8%) had cardiac instabilities, preoperatively. The mean modified Rankin Scale score was 2.7 on admission. Gross total resection was achieved in 52 patients (98.1%). Postoperatively, 23 patients (43.4%) had respiratory dysfunction, and 16 patients (30.2%) had dysphagia or cough. The mean follow-up duration was 35.7 months. At the last follow-up evaluation, the mean modified Rankin Scale score was 1.7, and 42 patients (84%) had favorable outcomes, with mRS scores ≤2. The conditions of the patients improved in 34 cases (68%), remained unchanged in 10 cases (20%), and worsened in 6 cases (12%) relative to the preoperative baseline. The independent adverse factors for long-term outcome were age ≥50 years and increased time of reservation of tracheal intubation after surgery. CONCLUSIONS: Surgical treatment of CMs involving the medulla oblongata was challenging, notably, perioperative respiratory dysfunction, with which patients tend to have unfavorable long-term outcomes, especially for elder patients.

Brainstem Cavernous Malformations: Surgical Indications Based on Natural History and Surgical Outcomes.

Cavernous malformations (CMs) are uncommon lesions occurring in the central nervous system, with an incidence of approximately 0.5% in the general population and constituting 5%-10% of all intracranial vascular malformations. Among CMs, prevalence within the brainstem as reported in the literature has ranged from 4% to 35%. With their precarious location and potentially devastating clinical events, brainstem CMs have attracted attention from neurosurgeons, and with these surgeons' unrelenting efforts, the microsurgical techniques to treat these lesions in the brainstem have greatly improved in recent decades. Although surgical outcomes reported in the literature have been satisfying, surgical intervention has become increasingly contraindicated because of the tendency for a benign clinical course in brainstem CMs, after weighing this fact against the high risk of surgical morbidity. Thus, it is advisable to operate on patients with symptomatic lesions abutting the pial or ependymal surface of the brainstem or where lesions are accessible to safe entry zones, which have caused more than 1 significantly symptomatic hemorrhage and can be defined as aggressive. However, treatment remains controversial for deep-seated lesions away from the surface of the brainstem or lesions that are inaccessible to safe entry zones. Other treatments, such as radiosurgery and medication, are still debatable, which might be as an alternative for lesions amenable to but at high risk with surgery.