scholarly journals The Molecular Landscape of Medulloblastoma in Teenagers and Young Adults

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 251
Author(s):  
Omar J. Mohammed ◽  
Maria Estevez Cebrero ◽  
Omar Ahmad ◽  
Andrew Peet ◽  
Richard G. Grundy ◽  
...  
Keyword(s):  
Young Adults ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Gene Signature ◽  
Group 4 ◽  
Teenagers And Young Adults ◽  
Molecular Landscape ◽  
Gene Expression Alterations ◽  
Computational Analyses ◽  
Multivariable Regression Models

Medulloblastoma (MB) is a childhood malignant brain tumour but also occurs in teenagers and young adults (TYA). Considering that MB is heterogeneous, this study aimed to define the molecular landscape of MBs in TYAs. We collated more than 2000 MB samples that included 287 TYA patients (13–24 years). We performed computational analyses consisting of genome-wide methylation and transcriptomic profiles and developed a prognostics model for the TYAs with MB. We identified that TYAs predominantly comprised of Group 4 (40%) and Sonic Hedgehog (SHH)-activated (33%) tumours, with Wingless-type (WNT, 17%) and Group 3 (10%) being less common. TYAs with SHH tumours displayed significantly more gene expression alterations, whereas no gene was detected in the Group 4 tumours. Across MB subgroups, we identified unique and shared sets of TYA-specific differentially methylated probes and DNA-binding motifs. Finally, a 22-gene signature stratified TYA patients into high- and low-risk groups, and the prognostic significance of these risk groups persisted in multivariable regression models (P = 0.001). This study is an important step toward delineating the molecular landscape of TYAs with MB. The emergence of novel genes and pathways may provide a basis for improved clinical management of TYA with MB.

scholarly journals Comprehensive Analysis of the Prognostic Significance of Hsa-miR-100-5p and Its Related Gene Signature in Stomach Adenocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Gaoming Wang ◽  
Ludi Yang ◽  
Miao Hu ◽  
Renhao Hu ◽  
Yongkun Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Development ◽  
Risk Groups ◽  
Gene Signature ◽  
Risk Scores ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Stomach Adenocarcinoma

Stomach adenocarcinoma (STAD) is one of the most common cancers in the world. However, the prognosis of STAD remains poor, and the therapeutic effect of chemotherapy and immunotherapy varies from person to person. MicroRNAs (miRNAs) play vital roles in tumor development and metastasis and can be used for cancer diagnosis and prognosis. In this study, hsa-miR-100-5p was identified as the only dysregulated miRNA in STAD samples through an analysis of three miRNA expression matrices. A weighted gene co-expression network analysis (WGCNA) was performed to select hsa-miR-100-5p-related genes. A least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to establish a miR-100-5p-related prognostic signature. Kaplan–Meier analyses, nomograms, and univariate and multivariate Cox regression analyses were used to evaluate the prognostic signature, which was subsequently identified as an independent risk factor for STAD patients. We investigated the tumor immune environment between low- and high-risk groups and found that, among component types, M2 macrophages contributed the most to the difference between these groups. A drug sensitivity analysis suggested that patients with high-risk scores may be more sensitive to docetaxel and cisplatin chemotherapy and that patients in the low-risk group may be more likely to benefit from immunotherapy. Finally, external cohorts were evaluated to validate the robustness of the prognostic signature. In summary, this study may provide new ideas for developing more individualized therapeutic strategies for STAD patients.

Frequency of risk groups in teenagers and young adults identified by the Findrisk survey

2009 ◽  
Vol 33 (3) ◽  
pp. 283
Author(s):  
H. Garcia-Alcala ◽  
O. Hirales-Tamez ◽  
C. Genestier-Tamborero
Keyword(s):  
Young Adults ◽  
Risk Groups ◽  
Teenagers And Young Adults

Unfavourable Outcome and Heterogeneity of Partner Chromosomes in Chronic Lymphocytic Leukemia with 14q32/IGH Translocations.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4686-4686
Author(s):  
Francesco Cavazzini ◽  
Jose A. Hernandez ◽  
Alessandro Gozzetti ◽  
Antonella Russo Rossi ◽  
Ruana Tiseo ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Hematological Parameters ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Lymphocytic Leukemia ◽  
Group 4 ◽  
Group 3 ◽  
The Difference ◽  
Group 2 ◽  
Group 1

Abstract Translocations of 14q32/IgH have a low incidence in CLL. Partner chromosomes and the prognostic significance are poorly defined. Four hundred thirty cases of CLL seen at the Hospitals of Ferrara, Salamanca and Siena between 1992 and 2006 were studied. Inclusion criteria were: diagnosis of CD5/CD19+ CLL with k/λ restriction, cytogenetic/FISH data, immunophenotypic data, complete hematological and clinical data. Lymphomas in leukemic phase were excluded. FISH was performed for 17p13/TP53, 11q22.3/ATM, 6q21, chr 12 centromere, 13q14 and 14q32/IGH. Patients with no detectable aberration or isolated 13q− were included into a favourable cytogenetic group (group 1), those with +12, 6q− or 1–2 aberrations into an intermediate risk group (group 2) and those with 17p−, 11q−, ≥ 3 aberrations into an unfavourable group (group 3). Cases with 14q32/IGH translocation as primary chromosome change represented a specific category (group 4) and were studied with FISH probes for the detection of partners (BCL1, BCL2, BCL3, BCL6, c-MYC, BCL11A, PAX5, CCND3, CDK6). One hundred eighty-six cases were allocated into group 1; 158 into group 2; 64 into group 3, and 22 into group 4. Additional aberrations were found in a minority of cells in 8 patients in group 4. Being the aim of the study to assess whether the 14q32/IGH translocation represented an unfavourable parameter as compared with cases in the favourable or intermediate cytogenetic risk groups, cases within group 3 were excluded from the analysis and the data presented here will refer to 366 patients belonging to groups 1,2 and 4. Translocation partners of 14q32/IGH were identified in 9/22 cases: 2p13/BCL11A, (n 1); 6p21/CCND3 (n 1); 7q21/CDK6 (n 1); 18q21/BCL2 (n 6). Thirteen cases did not show involvement of the loci studied. Cases with 14q32/IGH translocations were characterized by typical morphology and classical immunophenotype (score 4–5 in 92% of the cases). Unmutated IGVH genes were found in 11/18 cases tested (61%); ZAP-70 was positive in 3/5 cases tested. Median age was 63.5 years (range 18–97), male:female ratio 240/126; 345 patients were in Rai stage 0-II, 21 were in stage 3–4; CD38 was positive in 137/366 cases. There was no difference between groups 1,2 and 4 for age, stage, male:female ratio, hematological parameters at diagnosis, IGVH mutations and ZAP70. CD38 was more positive in group 4 than in group 1 (p=0.028). There was no difference in survival and treatment free interval (TFI) when comparing cases in group 4 with and without additional aberrations. Cases in group 4 had a shorter TFI and a shorter survival when compared with group 1 (p=0.02) and group 2 (p=0.02). The difference maintained its statistical significance at multivariate analysis for TFI (p=0.02) along with stage (p<0.0001) and CD38 positivity (p<0.0001) and for survival (p=0.02) along with sex (p=0.006) and stage (p=0.0001). In conclusion, the 14q32/IGH translocation in CLL shows heterogeneity of partner chromosomes and it represents a cytogenetic marker predicting for an evolutive form of CLL.

Epidemiological Characteristics of Meningococcal Infection in Moscow

2020 ◽  
Vol 19 (2) ◽  
pp. 56-62
Author(s):  
M. I. Gritsay ◽  
M. A. Koroleva ◽  
N. N. Fomkina ◽  
I. S. Koroleva
Keyword(s):  
Young Adults ◽  
Mortality Rate ◽  
Incidence Rate ◽  
Meningococcal Disease ◽  
Invasive Meningococcal Disease ◽  
Meningococcal Infection ◽  
Epidemic Process ◽  
Epidemiological Features ◽  
Teenagers And Young Adults ◽  
Epidemiological Characteristics

Aims. The purpose of this study was to identify current epidemiological features of meningococcal infection in Moscow.Materials and methods. Cases of invasive meningococcal disease in Moscow from 2014 to 2018 and the biomaterial from patients with an invasive meningococcal disease were analyzed.Results. The features of the epidemic process of meningococcal disease in Moscow were revealed: increasing in the incidence rate involving teenagers and young adults into the epidemic process; meningococcal strains of serogroups W and A increased in the etiology of the invasive meningococcal disease; high mortality rate.Conclusions. It seems reasonable to recommend vaccination against meningococcal disease by including adolescents, young adults and persons over 65 years old.

Gene Signature of m 6A regulators in Bladder Cancer: Prognostic Significance and Immune Implication

2019 ◽  
Author(s):  
Yuying Zhang ◽  
Baoyi Zhu ◽  
Yi Cai ◽  
Minghui He ◽  
Chonghe Jiang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Significance ◽  
Gene Signature

scholarly journals A 10-gene prognostic signature points to LIMCH1 and HLA-DQB1 as important players in aggressive cervical cancer disease

2021 ◽  
Author(s):  
Mari K. Halle ◽  
Marte Sødal ◽  
David Forsse ◽  
Hilde Engerud ◽  
Kathrine Woie ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Primary Tumour ◽  
Treatment Options ◽  
Prognostic Significance ◽  
Gene Signature ◽  
Prognostic Impact ◽  
Cancer Disease ◽  
Gene Set ◽  
Patient Cohort ◽  
Protein Levels

Abstract Background Advanced cervical cancer carries a particularly poor prognosis, and few treatment options exist. Identification of effective molecular markers is vital to improve the individualisation of treatment. We investigated transcriptional data from cervical carcinomas related to patient survival and recurrence to identify potential molecular drivers for aggressive disease. Methods Primary tumour RNA-sequencing profiles from 20 patients with recurrence and 53 patients with cured disease were compared. Protein levels and prognostic impact for selected markers were identified by immunohistochemistry in a population-based patient cohort. Results Comparison of tumours relative to recurrence status revealed 121 differentially expressed genes. From this gene set, a 10-gene signature with high prognostic significance (p = 0.001) was identified and validated in an independent patient cohort (p = 0.004). Protein levels of two signature genes, HLA-DQB1 (n = 389) and LIMCH1 (LIM and calponin homology domain 1) (n = 410), were independent predictors of survival (hazard ratio 2.50, p = 0.007 for HLA-DQB1 and 3.19, p = 0.007 for LIMCH1) when adjusting for established prognostic markers. HLA-DQB1 protein expression associated with programmed death ligand 1 positivity (p < 0.001). In gene set enrichment analyses, HLA-DQB1high tumours associated with immune activation and response to interferon-γ (IFN-γ). Conclusions This study revealed a 10-gene signature with high prognostic power in cervical cancer. HLA-DQB1 and LIMCH1 are potential biomarkers guiding cervical cancer treatment.

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