Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML
ONCOLOGY LETTERS
Authors: Zhang, Zhen; Zhao, Lin; Wei, Xijin; Guo, Qiang; Zhu, Xiaoxiao; Wei, Ran; Yin, Xunqiang; Zhang, Yunhong; Wang, Bin; Li, Xia
Abstract
Myeloid disorders, especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), cause significant mobility and high mortality worldwide. Despite numerous attempts, the common molecular events underlying the development of MDS and AML remain to be established. In the present study, 18 microarray datasets were selected, and a meta-analysis was conducted to identify shared gene signatures and biological processes between MDS and AML. Using NetworkAnalyst, 191 upregulated and 139 downregulated genes were identified in MDS and AML, among which, PTH2R, TEC, and GPX1 were the most upregulated genes, while MME, RAG1, and CD79B were mostly downregulated. Comprehensive functional enrichment analyses revealed oncogenic signaling related pathway, fibroblast growth factor receptor (FGFR) and immune response related events, interleukine-6/interferon signaling pathway, and B cell receptor signaling pathway', were the most upregulated and downregulated biological processes, respectively. Network based meta-analysis ascertained that HSP90AA1 and CUL1 were the most important hub genes. Interestingly, our study has largely clarified the link between MDS and AML in terms of potential pathways, and genetic markers, which shed light on the molecular mechanisms underlying the development and transition of MDS and AML, and facilitate the understanding of novel diagnostic, therapeutic and prognostic biomarkers.
Genetic Polymorphisms of Manganese-Dependent Superoxide Dismutase in Chagas Disease
INFECTIOUS DISEASES IN CLINICAL PRACTICE
Authors: Lassen, Oscar; Tabares, Sandra; Ojeda, Silvia; Dotto, Gladys; Bertolotto, Patricia; Sembaj, Adela
Abstract
Background: Infection with Trypanosoma cruzi triggers inflammatory mechanisms and induces the activity of manganese-dependent superoxide dismutase. Genetic single-nucleotide polymorphisms of this enzyme generate proteins with reduced enzymatic activity. The aims of this study were to determine the frequency of the polymorphisms Ala-9Val and Ile58Thr of the manganese-dependent superoxide dismutase gene in DNA from chagasic and nonchagasic patients and to establish a relationship between these polymorphisms with chronic chagasic cardiomyopathy. Methods: Two hundred fifty-eight unrelated patients underwent a general clinical examination and an electrocardiogram, a chest radiograph, and a 12-lead color Doppler echocardiogram were taken. Besides, we evaluate liver and renal function, lipid profile, and diagnosis of Chagas disease and genetic polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The patients were classified as nonchagasic group with negative serology for Chagas disease and the chagasic group with positive serology. This group was subdivided into asymptomatic when patients did not present abnormal cardiac symptoms and symptomatic if the chest radiograph, electrocardiogram, and/or color Doppler echocardiogram showed some alteration. Results: The female chagasic population shows a high frequency of the ile58ile genotype (P = 0.010; odds ratio, 3.3; 95% confidence interval, 1.35-8.38). Lower frequency of the ala-9ala genotype was detected in symptomatic Chagas patients (P = 0.001; odds ratio, 3.147; 95% confidence interval, 1.39-7.482). The analysis revealed an interaction between the ala/ala + val/val genotype (P = 0.0108) with the plasma concentration of low-density lipoprotein cholesterol in the symptomatic Chagas group. Conclusions: Our results show that the presence of the val allele is associated with chronic chagasic cardiomyopathy. The prognostic value of these results should be more deeply investigated.