The different role of YKL-40 in glioblastoma is a function of MGMT promoter methylation status.

Inter- and intratumoral heterogeneity is a hallmark of glioblastoma (GBM) that facilitates recurrence, treatment resistance, and worse prognosis. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a significant prognostic marker for Temozolomide (TMZ) resistance in GBM patients. YKL-40 is a molecular marker for the mesenchymal subtype of GBMs and is responsible for TMZ resistance. However, underlying mechanisms by which MGMT epigenetics impacts patient outcomes and the function of YKL-40 are not fully determined. Herein, we performed in vitro and in vivo experiments, six human IDH1/2 wild-type glioblastoma stem-like cells (GSCs) were established and studied to further determine a potential interaction of YKL-40 and MGMT promoter methylation. We demonstrated that YKL-40 functioned differently in human IDH1/2 wild-type GSCs. In MGMT promoter-methylated (MGMT-m) GSCs, it acted as a tumor suppressor gene. On the other hand, in MGMT promoter-unmethylated (MGMT-um) GSCs, it promoted tumorigenesis. Notably, the reason that YKL-40 played different roles in GSCs could not be interpreted by the molecular classification of each GSCs, but is a function of MGMT promoter methylation status and involves the RAS-MEK-ERK pathway. YKL-40 mediated TMZ sensitivity by activating DNA damage responses (DDRs) in MGMT-m GSCs, and it mediated resistance to TMZ by inhibiting DDRs in MGMT-um GSCs. Our report demonstrated that MGMT promoter methylation status might influence a gene's function in human cancer. Moreover, our data also highlight the point that gene function should be investigated not only according to the molecular tumor classification, but also the epigenetic signature.

Identification of differentially expressed genes and fusion genes associated with malignant progression of spinal cord gliomas by transcriptome analysis.

Glioma, the most common histological subtype of primary spinal cord tumors, is considered as a rare central nervous system neoplasm. In this study, 9 glioma samples (4 of grade II and 5 of grade IV with H3K27M positive) were analyzed to examine the molecular mechanisms underlying the malignant progression of gliomas, transcriptome sequencing. Differentially expressed genes (DEGs) in grade IV vs. grade II were analyzed by using the Limma package in R. Enrichment analysis was performed for the individual DEGs through VennPlex software and the Database for Annotation. Gene mutations and fusions were analyzed using the Genome Analysis Toolkit and STAR-Fusion. A total of 416 DEGs were identified in grade IV vs. grade II. Functional analysis of the DEGs showed that GALR1 and GRM5 of neuroactive ligand-receptor interactions signaling pathways may be relaed to malignant progression of gliomas. Further systematic transcriptional profiling identified 11 in-frame/frameshift gene fusions in the tumors. Notably, one novel gene fusions, GATSL2-GTF2I was detected in all of the grade II samples. In summary, the molecular alterations observed in glioma progression may improve the characterization of different human spinal cord glioma grades. The transcriptome analysis of intramedullary spinal cord glioma will provide a new candidate gene list for further mechanism research.

Primary spinal epidural cavernous hemangioma: clinical features and surgical outcome in 14 cases.

OBJECT: The aim of this study was to investigate the clinical characteristics, imaging features, differential diagnosis, treatment options, and prognosis for primary spinal epidural cavernous hemangiomas. METHODS: Fourteen patients with pathologically diagnosed non-vertebral origin cavernous hemangiomas who had undergone surgery at Beijing Tiantan Hospital between 2003 and 2012 were identified in the hospital's database. The patients' clinical data, imaging characteristics, surgical treatment, and postoperative follow-up were analyzed retrospectively. RESULTS: There were 9 males and 5 females with an average age of 51.64 years. The primary epidural cavernous hemangiomas were located in the cervical spine (2 cases), cervicothoracic junction (2 cases), thoracic spine (8 cases), thoracolumbar junction (1 case), and lumbar spine (1 case). Hemorrhage was confirmed in 4 cases during surgery. Preoperatively 5 lesions were misdiagnosed as schwannoma, 1 was misdiagnosed as a meningioma, and 1 was misdiagnosed as an arachnoid cyst. Preoperative hemorrhages were identified in 2 cases. Three patients had recurrent cavernous hemangiomas. The initial presenting symptoms were local pain in 5 cases, radiculopathy in 6 cases, and myelopathy in 3 cases. Upon admission, 1 patient had radicular symptoms and 13 had myelopathic symptoms. The average symptom duration was 18 months. All patients underwent surgery; complete resection was achieved in 8 cases, subtotal resection in 4 cases, and partial resection in 2 cases. Postoperative follow-up was completed in 10 cases (average follow-up 34 months); 1 patient died, 5 patients showed clinical improvement, and 4 patients remained neurologically unchanged. CONCLUSIONS: Total surgical removal of spine epidural cavernous hemangiomas with a chronic course is the optimum treatment and carries a good prognosis. Secondary surgery for recurrent epidural cavernous hemangioma is technically more challenging. In patients with profound myelopathy from acute hemorrhage, even prompt surgical decompression can rarely reverse all symptoms.

Surgical strategies and outcomes of spinal ependymomas of different lengths: analysis of 210 patients: clinical article.

OBJECT: The aim of this study was to investigate the surgical strategies and outcomes for spinal ependymomas of different lengths. METHODS: The authors used data from 210 patients with spinal ependymomas (WHO Grades II and III) in this 10-year retrospective study (January 1999 to December 2008), dividing them into 3 different groups according to length (spinal ependymomas < 5 cm, 5-10 cm, and > 10 cm). All patients underwent tumor resection. The basic characteristics of the patients were reviewed and the functional status was assessed using the McCormick classification. RESULTS: There were 89, 81, and 40 patients, respectively, in the 3 groups (< 5 cm, 5-10 cm, and > 10 cm). Grosstotal resections (GTRs) were performed in 172 patients (81.9% overall, or 86.5%, 79.0%, and 77.5% in the 3 groups, respectively). Subtotal and partial resections were achieved in 38 patients (18.1%). Eight patients with medulla oblongata or upper cervical cord tumors received a tracheotomy postoperatively. The follow-up period ranged from 56 to 176 months. One hundred thirty-five patients (76.7%) experienced improvement, (88.2%, 83.8%, and 34.4% in the < 5 cm, 5-10 cm, and > 10 cm groups, respectively). Thirty-three patients (18.8%) maintained their pretreatment status, and 8 patients (4.5%) showed deterioration following tumor resection at 6 months. Tumor recurrence or progression was observed in 6 (2.9%) of the 210 patients. Among the 6 patients, recurrent tumors were located in the conus (n = 3), thoracic (n = 1), and medullocervical cord (n = 2). CONCLUSIONS: Radical resection of spinal ependymomas could be performed in most patients, and the rate of GTR was significantly different in the different-length groups (< 10 cm vs > 10 cm, p = 0.032). Patients with longer tumors had worse surgical results compared with those with small tumors (p < 0.001), and more postoperative neuropathic pain and proprioceptive deficits could usually be observed in patients harboring larger tumors. Early diagnosis and timely operation are critical to achieving better neurological outcomes. For tumors with dense adhesions, complete removal should be performed cautiously because of the significant incidence of neurological deterioration.

[Outcome of microsurgical decompression combined with cervical artificial disc replacement].

OBJECTIVE: To study the microsurgical decompression combined with cervical artificial disc replacement clinical efficacy for the treatment of cervical spondylosis. METHODS: From January 2006 to November 2011, 21 cases of cervical spondylosis, totally 23 intervertebral spaces, were under the microscope disc decompression and cervical artificial disc replacement. There were 11 male and 10 female patients; aged from 28 to 60 years, with an average of 46.3 years. The diagnosis included 5 cases of nerve root type cervical spondylosis and 16 cases of cervical spondylotic myelopathy. Application of Bryan prosthesis treatment of 9 patients, a total of 10 intervertebral spaces; ProDisc-C prosthesis to treat 12 patients, a total of 13 intervertebral space. Following-up Japanese Orthopedic Association (JOA), neck disability index (NDI) and visual analogue scale (VAS) scores were recorded and compared with pre-operative scores by the paired t-test. RESULTS: The patients were followed up for 6 to 74 months, with an average of 27.7 months. Although a patient with spinal bony stenosis symptom improved, but not satisfied, and after the posterior decompression, who had a better prognosis. The remaining patients during follow-up symptoms were obvious improved, and the replacement segments were stable. There was no prosthesis subsidence and significantly offset. In 1 month post-operation and last follow-up compared with pre-operative scores, JOA (t = 9.195 and 17.070), NDI (t = 7.193 and 14.062) and VAS (t = 14.851 and 16.133) scores were significantly different (P < 0.05); and 1 month post-operation compared with last follow-up, JOA (t = 5.916), NDI (t = 7.722) and VAS (t = 4.564) scores were significantly different (P < 0.05). CONCLUSIONS: Cervical artificial disc replacement combined with microscopic decompression surgery can completely remove the oppression of nerve tissue caused by pressure, and the efficacy is more secure.