EFNA1 is a potential key gene that correlates with immune infiltration in low-grade glioma

EFNA1 is a key gene that is associated with the pathogenesis of several human cancers. However, the prognostic role of EFNA1 in many cancers and the relationship between EFNA1 and tumor-infiltrating lymphocytes in different cancers remain unclear.The expression levels of EFNA1 in 33 types of cancer in the TCGA (The Cancer Genome Atlas) database were collected via the UCSC Xena browser. The clinical data of LGG (low grade glioma) patients were downloaded from the TCGA database. The glioma data from the CGGA (Chinese Glioma Genome Atlas) database were also downloaded to verify the results. Kaplan–Meier and Cox regression analyses were used to investigate the prognostic value of EFNA1 in different cancers using R software. We verified the differential expression of EFNA1 in glioma and normal brain tissue via gene expression profiling interactive analysis. We evaluated the relationship between the expression level of EFNA1 and the clinicopathological features of LGG patients via the Wilcoxon signed-rank test. The immune infiltration levels were evaluated via tumor immune estimation resource (TIMER) and CIBERSORT, and the correlations between EFNA1 and immune cell levels were investigated via TIMER. Finally, we conducted gene set enrichment analysis (GSEA) to explore the potential mechanisms.Data from the TCGA database showed that EFNA1 was differentially expressed in many kinds of cancers when compared with normal tissues. Upregulated EFNA1 expression in esophageal carcinoma (ESCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and LGG correlated with shorter patient overall survival (OS) times. The Cox regression analysis revealed that the expression of EFNA1 was also a risk factor for the disease-specific survival (DSS) and progression-free interval (PFI) of LGG patients. The multiple Cox regression analysis revealed that EFNA1 was an independent prognostic factor for LGG patients. In addition, EFNA1 expression was increased in the WHO grade III group and the 1p19q non-codeletion group. Moreover, EFNA1 expression was positively correlated with the levels of infiltrating CD4+ T cells, myeloid dendritic cells and neutrophils in LGG. GSEA suggested that several GO and kyoto encyclopedia of genes and genomes (KEGG) items associated with nervous system function and apoptotic pathway were significantly enriched in the EFNA1-low and EFNA1-high expression phenotypes.EFNA1 may play a pivotal role in the development of LGG and may serve as a potential marker for LGG prognosis and therapy.     

基于TCGA数据库挖掘恶性脑胶质瘤乏氧与免疫微环境相关预后价值基因

目的 挖掘恶性脑胶质瘤中与乏氧诱导因子-1α（hypoxia inducible factor-1α,HIF-1α）表达存在相关性的免疫通路或基因,并进一步分析其对脑胶质瘤预后的影响。方法 从肿瘤基因组图谱（the cancer genome atlas,TCGA）数据库提取脑胶质瘤HIF-1α基因表达谱数据,采用R语言分析HIF-1α基因与其他基因之间的相关性,通过GO和KEGG数据库对差异表达基因进行功能注释,包括细胞组分、生物学过程、分子功能及相关信号通路。并采集了74例人脑胶质瘤组织进一步验证分析。结果 TCGA数据库中共收集到169例脑胶质瘤患者的数据,其中与HIF-1α基因有相关性的基因有455个。对455个满足条件的相关性基因进行GO和Pathway富集分析,共得到66个KEGG Pathway;最终发现基因TNFRSF1α的P值具有统计差异。进一步对比分析TCGA数据库169例脑胶质瘤患者与529例非肿瘤患者数据中TNFRSF1α表达的情况。结果 提示TNFRSF1α与HIF-1α在脑胶质瘤组织中显著高于癌旁组织。且人脑胶质瘤组织TNFRSF1α表达水平与胶质瘤的病理分级正相关。结论 KEGG通路发现TNFRSF1α基因与乏氧有关,提示TNFRSF1α基因可能与乏氧共同影响脑胶质瘤患者的预后。     

Two novel genetic variants in the STK38L and RAB27A genes are associated with glioma susceptibility

Glioma is the most common malignant primary brain tumors with poor prognosis. Genome wide association studies (GWAS) of glioma in populations with Western European ancestry were completed in the US and UK. However, our previous results strongly suggest the genetic heterogeneity could be important in glioma risk. To systematically investigate glioma risk–associated variants in Chinese population, we performed a multistage GWAS of glioma in the Han Chinese population, with a total of 3,097 glioma cases and 4,362 controls. In addition to confirming two associations reported in other ancestry groups, this study identified one new risk-associated locus for glioma on chromosome 12p11.23 (rs10842893, p_meta = 2.33x10-12, STK38L) as well as a promising association at 15q15-21.1 (rs4774756, p_meta = 6.12x10-8, RAB27A) in 3,097 glioma cases and 4,362 controls. Our findings demonstrate two novel association between the glioma risk region marked by variant rs10842893 and rs4774756) and glioma risk. These findings may advance the understanding of genetic susceptibility to glioma.     

Biofunctionalization of magnetite nanoparticles with stevioside: effect on the size and thermal behaviour for use in hyperthermia applications

Controlling the magnetic properties of a nanoparticle efficiently via its particle size to achieve optimized heat under alternating magnetic field is the central point for magnetic hyperthermia-mediated cancer therapy (MHCT). Here, we have shown the successful use of stevioside (a natural plant-based glycoside) as a promising biosurfactant to control the magnetic properties of Fe₃O₄ nanoparticles by controlling the particle size. The biocompatibility and cellular uptake efficiency by rat C6 glioma cells and calorimetric magnetic hyperthermia profile of the nanoparticles were further examined. Our finding suggests superior properties of stevioside-coated magnetite nanoparticles in comparison to polysorbate-80 and oleic acid coated nanomagnets as far as particle size reduction, biocompatibility, hyperthermic effect, and cellular uptake by the glioblastoma cancer cells are concerned. The stevioside-coated nanomagnets exhibiting the maximum temperature rise were further investigated as heating agents in in vitro magnetic hyperthermia experiments (405?kHz, 168?Oe), showing their efficacy to induce cell death of rat C6 glioma cells after 30?min at a target temperature T?=?43?°C.     

Correlation between the occurrence of 1H-MRS lipid signal, necrosis and lipid droplets during C6 rat glioma development

The aim of this study was to investigate the possible correlation between the 1H MRS mobile lipid signal, necrosis and lipid droplets in C6 rat glioma. First, the occurrence of necrosis and lipid droplets was determined during tumor development, by a histological analysis performed on 34 rats. Neither necrosis nor lipid droplets were observed before 18 days post-implantation. At later stages of development, both necrosis and lipid droplets were apparent, the lipid droplets being mainly located within the necrotic areas. Using a second group of eight rats, a temporal correlation was evidenced between mobile lipid signal detected by in vivo single-voxel one- (136 ms echo time) and two-dimensional J-resolved 1H MR spectroscopy, and the presence of necrosis and lipid droplets on the histological sections obtained from the brains of the same rats. Finally, spatial distribution of the mobile lipid signal was analyzed by chemical-shift imaging performed on a third group of eight animals, at the end of the tumor growth. The spectroscopic image corresponding to the resonance of mobile lipids had its maximum intensity in the center of the tumor where necrotic regions were observed on the histological sections. These necrotic areas contained large amounts of lipid droplets. All these results suggest that mobile lipids detected in vivo by 1H MRS (136 ms echo time) in C6 rat brain glioma arise mainly from lipid droplets located in necrosis.     

MRI结合人工智能技术预测弥漫性胶质瘤分子病理研究进展

分子病理指标对于诊断和治疗弥漫性胶质瘤(DG)具有关键作用。迅速发展的人工智能(AI)技术为预测DG分子病理和评估预后提供了客观、无创的工具。本文围绕MRI结合AI技术预测DG重要分子病理研究进展进行述评。     

富亮氨酸胶质瘤失活1蛋白抗体阳性边缘性脑炎临床分析及文献复习

目的：总结富亮氨酸胶质瘤失活1蛋白（LGI1）抗体阳性边缘性脑炎的临床和影像特点及诊疗预后。方法：报道我院1例LGI1抗体阳性相关边缘性脑炎并文献复习。结果：患者女性,60岁,表现为渐进性加重的记忆力减退、癫痫发作（全身强直阵挛发作,面-臂肌张力障碍发作）、低钠血症和轻度精神行为异常。颅 脑MRI-T2/Flair序列提示双侧颞叶（左侧为甚）内侧、海马异常高信号。脑脊液抗LGI1抗体阳性（++）。经激素治疗症状有所改善。检索既往报道LGI1抗体阳性边缘性脑炎患者237例,多数呈急性、亚急性起病,最常见是记忆障碍、癫痫（含面-臂肌张力障碍发作）和低钠血症,头颅MRI（特别是MRI-T2/Flair序列）显示单侧或者双侧海马区、颞叶异常多见,早期免疫治疗预后良好。结论：LGI1抗体阳性相关边缘性脑炎有其特有的临床特点,免疫治疗可明显改善患者预后。     

DWI、DTI联合常规MRI可提高高级别脑胶质瘤的诊断准确度

目的探讨扩散加权成像（DWI）、扩散张量成像（DTI）及常规MRI对高级别脑胶质瘤的诊断价值。方法选取2018年10月~2020年7月医院收治的65例脑胶质瘤患者作为研究对象。手术取病理组织标本,根据病理结果分为高级别脑胶质瘤组和低级别脑胶质瘤组。术前行MRI检查,扫描序列为T1WI、T2WI、DWI、DTI。分析不同级别脑胶质瘤MRI图像,比较不同级别脑胶质瘤的表观弥散系数（ADC）和各向异性分数（FA）值。分析瘤体ADC_DWI、ADC_DTI、FA诊断高级别脑胶质瘤阈值、敏感度及特异性。结果65例患者经术后病理检查均确诊为脑胶质瘤,其中低级别脑胶质瘤29例,高级别脑胶质瘤36例;不同级别脑胶质瘤瘤周ADC_DWI、ADC_DTI和FA值差异无统计学意义（P > 0.05）;不同级别脑胶质瘤瘤体FA值差异无统计学意义（P > 0.05）。高级别脑胶质瘤瘤体ADC_DWI和ADC_DTI值低于低级别脑胶质瘤（P < 0.05）。ADC_DWI、ADC_DTI、FA诊断高级别脑胶质瘤的AUC分别为0.775、0.817、0.716。DWI和DTI联合检测诊断高级别脑胶质瘤敏感度和特异度较高,AUC为0.903（P < 0.05）。结论常规MRI联合DWI、DTI有助于提高脑胶质瘤诊断和病理分级准确度。     

显微手术治疗脑胶质瘤的临床疗效探讨

目的对显微手术治疗脑胶质瘤的临床疗效及复发影响因素进行探讨。方法回顾性分析2010年1月至2013年1月运用显微手术治疗96例脑胶质瘤患者的临床资料,分析其手术疗效和复发影响因素。结果所选患者使用显微外科手术肿瘤全切74例,占77.1%,次全切19例,占19.8%,部分切除3例,占3.1%;出院时恢复良好57例(59.4%),基本好转26例(27.1%),显效8例(8.3%),进步5例(5.2%),无1例死亡;随访1~3年,所有患者获得随访,恢复正常者58例,占60.4%,38例复发,其中19例再次手术,死亡3例(非手术死亡),15例拒绝再次手术,死亡6例;低级别胶质瘤复发的发生率为15.4%,明显低于高级别胶质瘤的68.2%,差异有统计学意义(P0.05);年龄小于等于40岁的发生率为29.2%,明显低于大于40岁的50%,差异有统计学意义(P0.05);全切组的复发发生率为16.2%,明显低于次全切、部分切除的72.7%,差异有统计学意义(P0.05)。结论显微手术可明显提高肿瘤全切率,使手术疗效大大提高,从而提高生活质量,降低复发率及病死率;且术后的复发率与肿瘤组织分型、年龄、手术方式有关。