Identification of a glioma functional network from gene fitness data using machine learning.

Glioblastoma multiforme (GBM) is an aggressive form of brain tumours that remains incurable despite recent advances in clinical treatments. Previous studies have focused on sub-categorizing patient samples based on clustering various transcriptomic data. While functional genomics data are rapidly accumulating, there exist opportunities to leverage these data to decipher glioma-associated biomarkers. We sought to implement a systematic approach to integrating data from high throughput CRISPR-Cas9 screening studies with machine learning algorithms to infer a glioma functional network. We demonstrated the network significantly enriched various biological pathways and may play roles in glioma tumorigenesis. From densely connected glioma functional modules, we further predicted 12 potential Wnt/ß-catenin signalling pathway targeted genes, including AARSD1, HOXB5, ITGA6, LRRC71, MED19, MED24, METTL11B, SMARCB1, SMARCE1, TAF6L, TENT5A and ZNF281. Cox regression modelling with these targets was significantly associated with glioma overall survival prognosis. Additionally, TRIB2 was identified as a glioma neoplastic cell marker in single-cell RNA-seq of GBM samples. This work establishes novel strategies for constructing functional networks to identify glioma biomarkers for the development of diagnosis and treatment in clinical practice.

Laryngeal Extranodal Nasal-type Natural Killer/T-cell Lymphoma: A Clinicopathologic Study of 31 Cases in China.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL-N) initially presented in larynx is a rare condition without distinctive clinicopathologic features, with a challenging pathologic diagnosis. This study aimed to evaluate the clinicopathologic features and diagnosis of laryngeal ENKTL-N and spread awareness regarding ENKTL-N. A series of 31 cases of laryngeal ENKTL in one Chinese institution over a 9-year interval was retrospectively analyzed. Median age was 50 years (range, 13 to 77 y) with a male/female ratio of 5.2:1 (26/5). All patients initially presented with hoarseness and/or laryngalgia, and 10 patients (32.3%) experienced B symptoms. The supraglottic region was the most common site of occurrence (58.1%), the glottic area being the rarest site (6.5%). The mucosal squamous epithelium was detected in 26 specimens and pseudoepitheliomatous hyperplasia was observed in 8 cases (8/26, 30.8%). "Keratin-pearls" and a "pseudoinvasive" pattern were observed in 2 cases. Follow-up data were available for 26 patients (83.9%), the median survival duration was 9 months, and the overall survival rate at 5 years was 29.6%. Univariate analysis revealed that patients experiencing B symptoms (P=0.019) and age above 60 years had a significantly low survival (P=0.049) and that combined radiotherapy and chemotherapy prolongs overall survival (P<0.001). Laryngeal ENKTL-N is a rare entity with high aggressiveness and a poor prognosis. Multiple biopsies are usually required owing to secondary infection and massive necrosis. Laryngeal EKTL-N may mimic inflammatory lesions or well-differentiated squamous cell carcinoma. Therefore, clinical vigilance is essential to prevent misdiagnosis or a delayed diagnosis.

Mediastinal myelolipoma/extramedullary hematopoiesis presenting as a mass: rare differential diagnosis among mediastinal tumors.

OBJECTIVES: Mediastinal myelolipoma/extramedullary hematopoiesis presenting as a mass is infrequent and can lead to misdiagnosis. Here we describe a large series aiming to illustrate the clinicopathologic features. METHODS: We retrospectively searched mediastinal tumors and myelolipoma diagnosed at the Department of Pathology, West China Hospital from 2010 to 2015 and collected 14 mediastinal myelolipoma/extramedullary hematopoiesis cases presenting as an encapsulated mass among 1324 mediastinal mass diseases and 252 myelolipomas. RESULTS: There were 8 females and 6 males aged from 35 to 67 years old, most of whom were diagnosed incidentally. Cross-sectional imaging revealed encapsulated masses located in the posterior mediastinum with fat and soft tissue density showing heterogeneous enhancement. Radiologic diagnosis was neurogenic tumor for most cases. All but one patient underwent surgery and postoperative pathologic findings showed fat and hematologic elements. Considering the accompanying hematologic disorders, 5 patients were diagnosed as extramedullary hematopoiesis and the remaining 9 as myelolipoma. The average hematopoietic tissue percentage in extramedullary hematopoiesis was 70%, significantly higher than it was in myelolipoma. Patients showed no sign of recurrence or metastasis apart from the patient with hepatocellular carcinoma. CONCLUSIONS: Mediastinal myelolipoma/extramedullary hematopoiesis is a rare entity of solid tumors in the posterior mediastinum, affecting patients from their third decades, with no sex predilection and lacking unique clinical symptoms, and may be misdiagnosed as a malignant tumor on cross-sectional imaging. The final diagnosis relies on pathologic findings, and the precise classification of myelolipoma or extramedullary hematopoiesis relies on percentage of hematopoietic tissue and accompanying clinical symptoms. Surgery is the recommended treatment.

A GLO10 score for the prediction of prognosis in high grade gliomas.

Gliomas are the most common lethal brain tumours and remain great heterogeneity in terms of histopathology and clinical outcomes. Among them, glioblastomas are the most aggressive tumours that lead to a median of less than one-year survival in patients. Despite the little improvement of in diagnosis and treatments for last decades, there is an urgent need for prognostic markers to distinguish high- and low-risk patients before treatment.Here, we generated a list of genes associated with glioblastoma progressions and then performed a comprehensive statistical modelling strategy to derive a 10-gene (GLO10) score from genome wide expression profiles of a large glioblastoma cohort (n=844). Our study demonstrated that the GLO10 score could successfully distinguish high- and low-risk patients with glioblastomas regardless their traditional pathological factors. Validated in four independent cohorts, the utility of GLO10 score could provide clinicians a robust prognostic prediction tool to assess risk levels upfront treatments.

Gene expression profile for predicting survival of patients with meningioma.

Current staging methods are inadequate for predicting the overall survival of meningioma. DNA microarray technologies improve the understanding of tumour progression. We analysed genome wide expression profiles of 119 meningioma samples from two previous published DNA microarray studies. The Cox proportional hazards regression models were applied to identify overall survival related gene signature. A total of 449 genes (109 upregulated and 340 downregulated) were identified as differentially expressed in meningioma. Among these differentially expressed genes, 37 genes were identified to be related to meningioma overall survival. Our 37-gene signature is closely associated with overall survival among patients with meningioma. This gene expression profile could provide an optimization of the clinical management and development of new therapeutic strategies for meningioma.