Gene expression profile and bioinformatics analysis revealed key molecular characteristics of chordoma-before and after TNF- a treatment.
- 作者列表："Xu G","Liu C","Liang T","Zhang Z","Jiang J","Chen J","Xue J","Zeng H","Lu Z","Zhan X
BACKGROUND:Chordoma is a rare malignant tumor with limited treatment. Recent studies have shown that the proliferation and invasion ability of chordoma after Tumor necrosis factor alpha (TNF-α) treatment is enhanced, which may activate the gene pathway involved in the development of chordoma. This study tends to identify differentially expressed genes (DEGs) before and after treatment of TNF-α in chordoma cell line, providing a new target for future molecular therapy of chordoma. METHODS:The gene expression profile of GSE101867 was downloaded from the Gene Expression Omnibus database, and the differentially expressed genes were obtained using GEO2R. Based on the CLUEGO plugin in Cytoscape, DEGs functionality and enrichment analysis. A protein-protein interaction (PPI) network was constructed using Cytoscape based on data collected from the STRING online dataset. The Hub genes are selected from the CytoHubba, the first 20 genes that coexist with the KEGG tumor-related pathway. RESULTS:A total of 560 genes, including 304 up-regulated genes and 256 down-regulated genes, were selected as DEGs. Obviously, GO analysis shows that up-regulated and down-regulated DEGs are mainly enriched in biological processes such as synaptic tissue, cell adhesion, extracellular matrix organization and skeletal system development. DEGs are mainly enriched in tumor-associated pathways such as Pi3k-akt Signal path, Rap1 signal path. Three key genes were identified: PDGFRB, KDR, FGF2. All of these genes are involved in the tumor-associated pathways described previously. CONCLUSION:This study is helpful in understanding the molecular characteristics of chordoma development. Hub genes PDGFRB, KDR, FGF2 and pi3k-akt signaling pathway, Rap1 signaling pathway will become a new target for the future treatment of chordoma.
背景: 脊索瘤是一种罕见的恶性肿瘤，治疗有限。近年来研究表明，肿瘤坏死因子 α (TNF-α) 治疗后脊索瘤的增殖和侵袭能力增强，可能激活了参与脊索瘤发生发展的基因通路。本研究拟鉴定脊索瘤细胞系TNF-α 治疗前后的差异表达基因 (DEGs)，为今后脊索瘤的分子治疗提供新靶点。 方法: 从gene expression Omnibus数据库中下载GSE101867 的基因表达谱，利用GEO2R获得差异表达基因。基于Cytoscape中的CLUEGO插件，DEGs功能和富集分析。基于从字符串在线数据集收集的数据，使用Cytoscape构建了蛋白质-蛋白质相互作用 (PPI) 网络。Hub基因选自CytoHubba，前 20 个基因与KEGG肿瘤相关通路共存。 结果: 共选择 560 个基因，其中上调基因 304 个，下调基因 256 个作为DEGs。显然，GO分析表明，上调和下调的DEGs主要富集在突触组织、细胞黏附、细胞外基质组织和骨骼系统发育等生物过程中。DEGs主要富集于肿瘤相关通路，如Pi3k-akt信号通路、Rap1 信号通路等。确定了 3 个关键基因: PDGFRB、KDR、fgf2。所有这些基因都参与了前面描述的肿瘤相关通路。 结论: 本研究有助于了解脊索瘤发育的分子特征。Hub基因PDGFRB、KDR、FGF2 和pi3k-akt信号通路、Rap1 信号通路将成为未来治疗脊索瘤的新靶点。
METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.
METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.