RESUMEN
BACKGROUND/AIMS: CDH18 (cadherin 18) is specifically expressed in the central nervous system and associated with various neuropsychiatric disorders. In this study, the role of CDH18 in glioma carcinogenesis and progression was investigated. METHODS: The expression of CDH18 and its prognostic value in patients with gliomas were analyzed in public database and validated by real-time PCR/immunohistochemical staining (IHC) in our cohort. CCK-8 assay, transwell migration assay, wound healing assay, clonogenic assay and tumorigenicity assay were used to compare the proliferation, invasion and migration ability of glioma cells with different expressions of CDH18. iTRAQ-based quantitative proteomic analysis were used to reveal the downstream target of CDH18. Rescue experiments were conducted to further validate the relationship between UQCRC2 and CDH18. RESULTS: The expression of CDH18 was depressed in a ladder-like pattern from normal tissues to WHO IV gliomas, and was an independent prognostic factor in TCGA (The Cancer Genome Atlas), CGGA (the Chinese glioma genome-atlas) and our glioma cohorts (n=453). Functional experiments in vitro and in vivo demonstrated that CDH18 inhibited invasion/migration, enhanced chemoresistance and suppressed tumorigenicity of glioma cells. UQCRC2 was identified as the downstream target of CDH18 by proteomic analysis. The expression of UQCRC2 was gradually absent as the WHO grades of gliomas escalated and was positively correlated with the expression of CDH18. Furthermore, in vitro assays demonstrated that down-regulation of UQCRC2 partly reversed the inhibition of invasion/migration ability and chemoresistance in CDH18 overexpressed glioma cell lines. Survival analysis demonstrated that combined CDH18/UQCRC2 biomarkers significantly influenced the prognosis of glioma patients. CONCLUSIONS: The present research demonstrated that CDH18 exerted its tumor-suppressor role via UQCRC2 in glioma cells and CDH18 might serve as a therapeutic target for treating gliomas.
Asunto(s)
Neoplasias Encefálicas/patología , Cadherinas/metabolismo , Complejo III de Transporte de Electrones/metabolismo , Glioma/patología , Anciano , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/metabolismo , Cadherinas/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dacarbazina/análogos & derivados , Dacarbazina/farmacología , Resistencia a Antineoplásicos , Complejo III de Transporte de Electrones/antagonistas & inhibidores , Complejo III de Transporte de Electrones/genética , Regulación Neoplásica de la Expresión Génica , Glioma/metabolismo , Humanos , Ratones , Ratones Desnudos , Persona de Mediana Edad , Proteínas Mitocondriales , Pronóstico , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , TemozolomidaRESUMEN
During neurological surgery, neurosurgeons have to transform the two-dimensional (2D) sectional images into three-dimensional (3D) structures at the cognitive level. The complexity of the intracranial structures increases the difficulty and risk of neurosurgery. Mixed reality (MR) applications reduce the obstacles in the transformation from 2D images to 3D visualization of anatomical structures of central nervous system. In this study, the holographic image was established by MR using computed tomography (CT), computed tomography angiography (CTA) and magnetic resonance imaging (MRI) data of patients. The surgeon's field of vision was superimposed with the 3D model of the patient's intracranial structure displayed on the mixed reality head-mounted display (MR-HMD). The neurosurgeons practiced and evaluated the feasibility of this technique in neurosurgical cases. We developed the segmentation image masks and texture mapping including brain tissue, intracranial vessels, nerves, tumors, and their relative positions by MR technologies. The results showed that the three-dimensional imaging is in a stable state in the operating room with no significant flutter and blur. And the neurosurgeon's feedback on the comfort of the equipment and the practicality of the technology was satisfactory. In conclusion, MR technology can holographically construct a 3D digital model of patient's lesions and improve the anatomical perception of neurosurgeons during craniotomy. The feasibility of the MR-HMD application in neurosurgery is confirmed.
Asunto(s)
Craneotomía/métodos , Holografía/métodos , Cirugía Asistida por Computador/métodos , Anciano , Neoplasias Encefálicas/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodosRESUMEN
AIM: To investigate the expression of BMP-2 protein and mRNA in glioma, and evaluate its clinical significance in clinicopathological status of patients with glioma. METHODS: BMP-2 protein and mRNA expression in 88 patients with glioma were examined by SABC immunohistochemistry and RT-PCR, respectively. RESULTS: The positive expression rate of BMP-2 protein in glioma tissues were 78.40% (69/88), which was significantly higher (P<0.01) than that in normal brain tissues [3% (6/20)]. The expression of BMP-2 protein and mRNA in gliomas of grade III-IV was also significantly higher than that in gliomas of grade I-II. CONCLUSION: BMP-2 expression in cancerous tissues may play an important role in the progression of glioma, which may help to predict patients' prognosis as a tumor marker.