scholarly journals CCT6A, a Novel Prognostic Biomarker for Ewing's Sarcoma

2020 ◽  
Author(s):  
Jie Jiang ◽  
Chong Liu ◽  
Guoyong Xu ◽  
Tuo Liang ◽  
Chaojie Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Ewing Sarcoma ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
High Expression ◽  
P Value ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract Background: Ewing's sarcoma (ES) is the second most prevalent malignancy among bone tissue tumors, and there is no adequate prognosis biomarker. The protein encoded by CCT6A is a molecular chaperone. Early studies have suggested that CCT6A is involved in the development of many cancers, however, there is no clear evidence of a role for CCT6A in ES.Methods: In this study, we performed a bioinformatics analysis of 32 Ewing sarcoma specimens from the GSE17618 dataset for differences in gene expression and overall survival, event-free survival, and gene expression in different subgroups. Results: After three screenings, we identified CCT6A as highly correlated with Ewing's sarcoma prognosis. Survival analysis showed low overall survival (OS) for CCT6A high expression (P=0.024). On the other hand, Cox regression analysis showed that CCT6A expression, event-free survival (EFS), and age were strongly associated with the prognosis of Ewing sarcoma, identified as independent poor prognostic biomarkers. (CCT6A: P=0.015; Age: P-value=0.026; EFS: P-value=0.001). Conclusion: The expression level of CCT6A is strongly associated with the prognosis of Ewing's sarcoma. High expression of the CCT6A gene may serve as a biomarker for poor prognosis in patients with Ewing's sarcoma.

CCT6A, a novel prognostic biomarker for Ewing's sarcoma

2020 ◽  
Author(s):  
Jie Jiang ◽  
Chong Liu ◽  
Guoyong Xu ◽  
Tuo Liang ◽  
Chaojie Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Ewing Sarcoma ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
High Expression ◽  
P Value ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract Background Ewing's sarcoma (ES) is the second most prevalent malignancy among bone tissue tumors, and there is no adequate prognosis biomarker. The protein encoded by CCT6A is a molecular chaperone. Early studies have suggested that CCT6A is involved in the development of many cancers, however, there is no clear evidence of a role for CCT6A in ES. Methods In this study, we performed a bioinformatics analysis of 32 Ewing sarcoma specimens from the GSE17618 dataset for differences in gene expression and overall survival, event-free survival, and gene expression in different subgroups. Results After three screenings, we identified CCT6A as highly correlated with Ewing's sarcoma prognosis. Survival analysis showed low overall survival (OS) for CCT6A high expression (P = 0.024). On the other hand, Cox regression analysis showed that CCT6A expression, event-free survival (EFS), and age were strongly associated with the prognosis of Ewing sarcoma, identified as independent poor prognostic biomarkers. (CCT6A: P = 0.015; Age: P-value = 0.026; EFS: P-value = 0.001). Conclusion The expression level of CCT6A is strongly associated with the prognosis of Ewing's sarcoma. High expression of the CCT6A gene may serve as a biomarker for poor prognosis in patients with Ewing's sarcoma.

Neoadjuvant Chemotherapy for Peripheral Malignant Neuroectodermal Tumor of Bone: Recent Experience at the Istituto Rizzoli

2000 ◽  
Vol 18 (4) ◽  
pp. 885-885 ◽  
Author(s):  
Gaetano Bacci ◽  
Stefano Ferrari ◽  
Franco Bertoni ◽  
Davide Donati ◽  
Patrizia Bacchini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Neural Differentiation ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Local Treatment ◽  
Neuroectodermal Tumor ◽  
Recent Experience ◽  
Event Free Survival ◽  
Free Survival

PURPOSE: The results achieved in 44 patients with nonmetastatic peripheral neuroectodermal tumor (PNET) of bone treated with neoadjuvant chemotherapy are reported. PATIENTS AND METHODS: A six-drug regimen of chemotherapy (vincristine, doxorubicin, dactinomycin, cyclophosphamide, ifosfamide, and etoposide) was administered to all patients. Local treatment consisted of surgery in 20 patients, surgery followed by radiotherapy in 13, and radiotherapy only in 11. RESULTS: At a mean follow-up of 4.5 years (range, 2 to 7 years), 23 patients (52%) remain event-free, 20 have relapsed (45%), and one has died of chemotherapy-related toxicity. The 5-year event-free survival and overall survival were 54.2% and 62.7%, respectively. To assess the prognostic significance of neural differentiation in the family of Ewing’s sarcoma, these results have been compared with the outcomes of 138 concomitant patients with typical Ewing’s sarcoma (TES) who were treated according to the same protocol. Of these, 103 (75%) remained continuously event-free, 34 (24%) relapsed, and one died of chemotherapy-related toxicity. It follows that PNET patients treated with this chemotherapy regimen have a significantly worse prognosis than typical ES patients (5-year event-free survival, 54.2% v 70.6%, P < .012; 5-year overall survival, 62.7% v 78.3%, P < .002). CONCLUSION: The authors conclude that studies into new adjuvant therapy for Ewing’s sarcoma modulated according to risk of relapse should also consider neural differentiation as a risk factor.

scholarly journals High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008

2019 ◽  
Vol 37 (34) ◽  
pp. 3192-3202 ◽  
Author(s):  
Uta Dirksen ◽  
Bernadette Brennan ◽  
Marie-Cécile Le Deley ◽  
Nathalie Cozic ◽  
Henk van den Berg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ewing Sarcoma ◽  
High Dose Chemotherapy ◽  
P Value ◽  
High Dose ◽  
Event Free Survival ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Significant Difference ◽  
Pleural Metastases

PURPOSE The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

scholarly journals Prognostic roles of microRNA 143 and microRNA 145 in colorectal cancer: A meta-analysis

2019 ◽  
Vol 34 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Chenyao Li ◽  
Guoqiang Yan ◽  
Libin Yin ◽  
Tao Liu ◽  
Chao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hazard Ratio ◽  
High Expression ◽  
Cochrane Library ◽  
Event Free Survival ◽  
Free Survival ◽  
High Event ◽  
Low Expression

Background: A systematic analysis was conducted to clarify the relationship between miR-143/145 and the prognosis of colorectal cancer. Materials and methods: We searched four databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. We extracted and estimated the hazard ratios for survival outcomes, which compared low and high expression levels of miR-143/145 in colorectal cancer patients in the available studies. Each individual hazard ratio was used to calculate the pooled hazard ratio. Results: A total of 17 articles including 5128 patients were ultimately included. The results showed that there was no significant difference between low expression and high expression of miR-143 in the overall survival of colon cancer patients. However, low expression of miR-143 was significantly associated with high event-free survival (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.40, 0.88). Low expression of miR-145 was associated with poor prognosis of patients (HR 1.92; 95% CI 1.45, 2.54); those with low expression of miR-145 were at 1.92-fold higher risk for short-term overall survival than those with high expression of miR-145. MiR-145 was an unfavorable factor for the prognosis of colorectal cancer. There were no significant differences between low expression of miR-145 and high expression of miR-143 in event-free survival. Conclusion: miR-143 and miR-145 have promising prognostic value for colorectal cancer. Low expression of miR-143 can predict high event-free survival, and low expression of miR-145 can predict poor overall survival.

scholarly journals Individualized Prediction of Overall Survival for Metastatic Ewing sarcoma of Bone

2021 ◽  
Author(s):  
wang chengwei
Keyword(s):  
Overall Survival ◽  
Ewing Sarcoma ◽  
Classification System ◽  
Ewing’S Sarcoma ◽  
Prediction Models ◽  
Ewing's Sarcoma ◽  
Characteristic Curve ◽  
Treatment Method ◽  
Risk Classification ◽  
Cox Analysis

Abstract Background: Few models have been used to estimate the survival rate of patients metastatic Ewing sarcoma of bone are scarce. We aimed to develop nomograms for predicting 3-, 5-year survival for these patients.Methods: We extracted 686 cases of metastatic Ewing's sarcoma diagnosed between 1973 and 2016 from the Surveillance, Epidemiological and End Results (SEER) database. Univariate and multivariate Cox analysis were used to determine independent prognostic factors. The nomograms are based on the results of multivariate Cox analysis. We also evaluate the performance of these prediction models through the analysis of time-dependent receiver operating characteristic curve, concordance index, calibration curve and decision curve.Results: Age, surgery, tumor size, treatment method and chemotherapy were considered to be important predictors of overall survival of bone metastatic Ewing's sarcoma. Based on these factors, the nomogram models were established and verified internally. These models have good identification and calibration characteristics. A risk classification system based on nomogram has also been constructed to promote risk stratification of metastatic Ewing's sarcoma and to optimize clinical management.Conclusions: We developed the first nomograms and corresponding risk classification system to predict the survival of patients with bone metastatic Ewing's sarcoma. These easy-to-use tools can help oncologists and surgeons make accurate survival assessments.

High expression of nucleoside transporter hENT1 predicts a worse event-free survival in relapsed/refractory Hodgkin lymphoma patients treated with gemcitabine, vinorelbine, and liposomal doxorubicin—A CALGB 59804 correlative study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7581-7581
Author(s):  
R. Lai ◽  
E. D. Hsi ◽  
J. Mackey ◽  
S. Jung ◽  
J. L. Johnson ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Liposomal Doxorubicin ◽  
Cox Regression ◽  
Nucleoside Analogs ◽  
Hazard Ratio ◽  
High Expression ◽  
Event Free Survival ◽  
Fixed Tissue ◽  
Free Survival ◽  
Cox Regression Analysis

7581 Background: CALGB 59804 was a phase I/II trial of gemcitabine, vinorelbine, and liposomal doxorubicin (GVD) for pts with relapsed Hodgkin lymphoma (HL). Overall response rate (RR) was 70% (manuscript in review). Plasma membrane nucleoside transporters such as hENT1 are important in transporting nucleoside analogs into cells to exert their pharmacologic effects. We hypothesized high hENT1 expression would predict better RR and outcome in pts treated with GVD. Methods: 58 of 91 pts enrolled in CALGB 59804 had sufficient tissue for study; 31 relapse biopsies and 27 initial diagnosis biopsies. Expression of hENT1 was evaluated by immunohistochemistry in formalin fixed tissue and scored independently by two hematopathologists (RL and EH) blinded to the clinical outcomes. Positivity for hENT1 was defined as >25% of Reed-Sternberg (RS) cells expressing hENT1. Expression was correlated with clinical factors, including IPS at relapse, as well as the overall (OS) and event-free survival (EFS). Results: Expression of hENT1 in RS cells was heterogeneous among cases. 28/58 cases (48%) were hENT1-positive. hENT1-expression was not associated with age, gender, stage, IPS (≤2 or >2), or maximum toxicity grade (≤2 or >2). Compared to hENT1-negative pts, hENT1-positive pts were less likely to have complete or partial response (19/30, 63% versus 22/28, 76%, P=0.20, chi square). hENT1 expression was not significantly associated with OS (P=0.18). Univariate log-rank analysis showed hENT1 positivity and IPS >2 correlated significantly with a lower EFS (P=0.05, and P=0.03, respectively). Multivariate Cox regression analysis confirmed that IPS >2 and hENT1 positivity were independent predictors of EFS (Hazard ratio 2.16, 95%CI 1.08–4.35, P=0.03; and Hazard ratio 2.10, 95% CI 1.06–4.19, P=0.03, respectively). P-values are two-sided. Conclusions: Contrary to our hypothesis, there is an inverse relationship between EFS and hENT1 expression in relapsed HL pts treated with GVD. High expression of hENT1 did not identify gemcitabine-sensitive disease, but may identify a biologically aggressive and/or treatment refractory subtype of HL. No significant financial relationships to disclose.

scholarly journals Identification of aberrantly methylated-differentially expressed genes and potential agents for Ewing’s sarcoma

2020 ◽  
Author(s):  
Shijie Gao ◽  
Guowang Li ◽  
Hao Yu ◽  
Shiyang Yuan ◽  
Wenxiang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Differentially Expressed ◽  
High Expression ◽  
Hub Genes ◽  
Low Expression

Abstract Background DNA methylation is a common epigenetic regulatory way, and it plays a critical role in various human diseases. However, the potential role of how DNA methylation impacts Ewing’s sarcoma (ES) is not clear. This study aimed to explore the regulatory role of DNA methylation in ES. Methods The microarray data of gene expression and methylation were downloaded from Gene Expression Omnibus (GEO) database, and analyzed via GEO2R. Venn analysis was then applied to identify aberrantly methylated differentially expressed genes (DEGs). Subsequently, Function and pathway enrichment analysis was conducted. Protein-protein interaction (PPI) network was constructed. Hub genes were determined. Besides, a connectivity map (CMap) analysis was performed to screen bioactive compounds for ES treatment. Results A total of 135 hypomethylated high expression genes and 523 hypermethylated low expression genes were identified. The hypomethylated high expression genes were enriched in signal transduction and the apoptosis process. Meanwhile, hypermethylated low expression genes were related to DNA replication and transcription regulation. We next determined 10 hub genes through PPI analysis, among them, C3, TF, and TCEB1 might serve as diagnostic and therapeutic targets. Furthermore, CMap analysis revealed 6 chemicals as potential options for ES treatment. Conclusions For the first time, we jointly analyzed gene profiling and methylation data about ES. The introduction of DNA methylation characteristics over DEGs is helpful to understand the pathogenesis of ES. The identified hub aberrantly methylated DEGs and chemicals might provide some novel insights on ES treatment.

scholarly journals Identification of Aberrantly Methylated-differentially Expressed Genes and Potential Agents for Ewing’s Sarcoma

2021 ◽  
Author(s):  
Shijie Gao ◽  
Guowang Li ◽  
Hao Yu ◽  
Shiyang Yuan ◽  
Wenxiang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Differentially Expressed ◽  
High Expression ◽  
Hub Genes ◽  
Low Expression

Abstract Background: DNA methylation is a common epigenetic regulatory way, and it plays a critical role in various human diseases. However, the potential role of how DNA methylation impacts Ewing’s sarcoma (ES) is not clear. This study aimed to explore the regulatory role of DNA methylation in ES.Methods: The microarray data of gene expression and methylation were downloaded from Gene Expression Omnibus (GEO) database, and analyzed via GEO2R. Venn analysis was then applied to identify aberrantly methylated differentially expressed genes (DEGs). Subsequently, Function and pathway enrichment analysis was conducted. Protein-protein interaction (PPI) network was constructed. Hub genes were determined. Besides, a connectivity map (CMap) analysis was performed to screen bioactive compounds for ES treatment.Results: A total of 135 hypomethylated high expression genes and 523 hypermethylated low expression genes were identified. The hypomethylated high expression genes were enriched in signal transduction and the apoptosis process. Meanwhile, hypermethylated low expression genes were related to DNA replication and transcription regulation. We next determined 10 hub genes through PPI analysis, among them, C3, TF, and TCEB1 might serve as diagnostic and therapeutic targets. Furthermore, CMap analysis revealed 6 chemicals as potential options for ES treatment. Conclusions: For the first time, we jointly analyzed gene profiling and methylation data about ES. The introduction of DNA methylation characteristics over DEGs is helpful to understand the pathogenesis of ES. The identified hub aberrantly methylated DEGs and chemicals might provide some novel insights on ES treatment.

scholarly journals Meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.

2020 ◽  
Author(s):  
Kazuhiro Tanaka ◽  
Masanori Kawano ◽  
Tatsuya Iwasaki ◽  
Ichiro Itonaga ◽  
Hiroshi Tsumura
Keyword(s):  
Overall Survival ◽  
Randomized Controlled Trials ◽  
Ewing Sarcoma ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Randomized Controlled ◽  
Hazard Ratios

Abstract Background In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the surrogacy of EFS for OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach. Methods We identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated using weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2). Results A total of 3,612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis revealed that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929). Conclusions Overall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. EFS may be useful as a surrogate endpoint in RCTs of ES, and the surrogacy of EFS is worth verifying using individual data.

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