Dataset Information

Molecular Mechanism of Telomere Length Dynamics and Its Prognostic Value in Pediatric Cancers.

ABSTRACT: BACKGROUND:We aimed to systematically evaluate telomere dynamics across a spectrum of pediatric cancers, search for underlying molecular mechanisms, and assess potential prognostic value. METHODS:The fraction of telomeric reads was determined from whole-genome sequencing data for paired tumor and normal samples from 653 patients with 23 cancer types from the Pediatric Cancer Genome Project. Telomere dynamics were characterized as the ratio of telomere fractions between tumor and normal samples. Somatic mutations were gathered, RNA sequencing data for 330 patients were analyzed for gene expression, and Cox regression was used to assess the telomere dynamics on patient survival. RESULTS:Telomere lengthening was observed in 28.7% of solid tumors, 10.5% of brain tumors, and 4.3% of hematological cancers. Among 81 samples with telomere lengthening, 26 had somatic mutations in alpha thalassemia/mental retardation syndrome X-linked gene, corroborated by a low level of the gene expression in the subset of tumors with RNA sequencing. Telomerase reverse transcriptase gene amplification and/or activation was observed in 10 tumors with telomere lengthening, including two leukemias of the E2A-PBX1 subtype. Among hematological cancers, pathway analysis for genes with expressions most negatively correlated with telomere fractions suggests the implication of a gene ontology process of antigen presentation by Major histocompatibility complex class II. A higher ratio of telomere fractions was statistically significantly associated with poorer survival for patients with brain tumors (hazard ratio = 2.18, 95% confidence interval = 1.37 to 3.46). CONCLUSION:Because telomerase inhibitors are currently being explored as potential agents to treat pediatric cancer, these data are valuable because they identify a subpopulation of patients with reactivation of telomerase who are most likely to benefit from this novel therapeutic option.

SUBMITTER: Wang Z

PROVIDER: S-EPMC7357329 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Molecular Mechanism of Telomere Length Dynamics and Its Prognostic Value in Pediatric Cancers.

Wang Zhaoming Z Rice Stephen V SV Chang Ti-Cheng TC Liu Yu Y Liu Qi Q Qin Na N Putnam Daniel K DK Shelton Kyla K Lanctot Jennifer Q JQ Wilson Carmen L CL Ness Kirsten K KK Rusch Michael C MC Edmonson Michael N MN Wu Gang G Easton John J Kesserwan Chimene A CA Downing James R JR Chen Xiang X Nichols Kim E KE Yasui Yutaka Y Robison Leslie L LL Zhang Jinghui J

Journal of the National Cancer Institute 20200701 7

<h4>Background</h4>We aimed to systematically evaluate telomere dynamics across a spectrum of pediatric cancers, search for underlying molecular mechanisms, and assess potential prognostic value.<h4>Methods</h4>The fraction of telomeric reads was determined from whole-genome sequencing data for paired tumor and normal samples from 653 patients with 23 cancer types from the Pediatric Cancer Genome Project. Telomere dynamics were characterized as the ratio of telomere fractions between tumor and n ...[more]

PMID: 31647544

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Project description:Introduction: Severe trauma accounts for a great number of deaths among children and adolescents. The diagnostic value of troponin serum levels of severely injured patients has been reported for adults, but data on pediatric polytrauma (PT) are scarce. Therefore, we conducted a retrospective monocentered study analyzing the prognostic value of troponin T (TnT) in pediatric trauma patients at the time point of hospital admission. Methods: Data of 88 polytraumatized pediatric patients admitted to the emergency room of the University Hospital of Ulm, Germany, between 2007 and 2016 were analyzed retrospectively. The data source was the written and digital patient records. Interleukin-6 (IL-6), creatine kinase activity (CK activity), and lactate and TnT levels were measured by a certified clinical diagnostic laboratory; and patients were stratified for the Injury Severity Score (ISS). The prognostic value for lung contusion, organ dysfunction, and fatal outcome was statistically explored. The study was approved by the independent ethical committee of the University of Ulm (#44/18). Results: TnT levels were significantly increased in patients after severe PT compared with mild or moderate trauma severity as assessed by ISS values. Patients with TnT levels above the cutoff showed significantly increased levels of IL-6 and CK activity and a significantly prolonged stay in the intensive care unit. However, TnT levels did not correlate with absolute ISS values. TnT levels were significantly increased in patients with chest trauma and lung contusion. The incidence of lung contusion was associated with elevation of TnT. So was the onset of organ dysfunction, defined as a Sequential Organ Failure Assessment (SOFA) score ? 2 and fatal outcome, with a significant enhancement of plasma levels in children with organ dysfunction and in non-survivors. Conclusion: These descriptive data suggest that evaluation of TnT on admission of multiply injured children may help in predicting severity of injury and mortality in the clinical course after trauma and thus may be a useful addition to established prognostic parameters in the future.

Project description:Background: Many studies manifested miRNA-628 (miR-628) was deregulated in various cancers, indicating that miR-628 might serve as a novel biomarker of cancer diagnosis and prognosis, but it's role was still uncertain. This study aimed to evaluate the value of miR-628 in various cancers for diagnosis and prognosis, as well as its predictive power in combination biomarkers. Materials and Methods: A literature search was performed using Medline (via PubMed), Embase, Web of Science databases, and Ovid platform up to November 2017. Meta-analysis was performed to provide summative outcomes. Quality assessment of each included study was performed. Results: Twelve articles with 20 studies were included in our meta-analysis, including 8 articles with 15 studies for diagnostic meta-analysis and 4 articles with 5 studies for prognostic meta-analysis. For the diagnostic meta-analysis of miR-628 alone, the overall pooled results for sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve (AUC) were 0.81 (95% CI: 0.62-0.91), 0.72 (95% CI: 0.48-0.88), 2.90 (95% CI: 1.50-5.40), 0.27 (95% CI: 0.14-0.50), 11.0 (95% CI: 4.00-25.00), and 0.84 (95% CI: 0.80-0.87), respectively. For the diagnostic meta-analysis of miR-628-related combination biomarkers, the above six parameters were 0.89 (95% CI: 0.84-0.92), 0.93 (95% CI: 0.82-0.97), 12.30 (95% CI: 4.70-32.50), 0.12 (95% CI: 0.08-0.19), and 100.00 (95% CI: 28.00-354.00), 0.93 (95% CI: 0.90-0.95), respectively. For the prognostic meta-analysis, patients with lower miR-628 had significant shorter overall survival than high expression of miR-628 (HR = 1.553, 95% CI: 1.041-2.318, z = 2.16, P = 0.031). Conclusions: This study confirms that miR-628 may be a promising biomarker for cancer diagnosis and prognosis. Expertly, microRNAs combination biomarkers could be a new alternative for clinical application.

Dataset Information

Molecular Mechanism of Telomere Length Dynamics and Its Prognostic Value in Pediatric Cancers.

Publications

Molecular Mechanism of Telomere Length Dynamics and Its Prognostic Value in Pediatric Cancers.

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