RESUMO
The aim of this study was to screen for key biomarkers of osteosarcoma (OS) by tracking altered modules. Protein-protein interaction (PPI) networks of OS and normal groups were constructed and re-weighted using the Pearson correlation coefficient (PCC), respectively. The condition-specific modules were explored from OS and normal PPI networks using a clique-merging algorithm. Altered modules were identified by a maximum weight bipartite-matching method. The important biological pathways in OS were identified by a pathway-enrichment analysis using genes from disrupted modules. The most important genes in these pathways were selected as key biomarkers. Finally, the mRNA and protein expressions of hub genes in OS bone tissues were analyzed using reverse transcription-polymerase chain reaction and western blotting, respectively. We identified 703 and 2270 modules in normal and disease networks, respectively; 150 altered modules were identified from among these and explored. We identified 10 important pathways based on gene pairs with altered PCC > 1 in the disrupted modules (P < 0.01), and PCNA, ATP6V1C2, ATP6V1G3, FEN1, CDC7, and RPA3 (expressed in these pathways) were selected as key genes of OS. We observed that these genes (and the proteins they encoded) were differentially expressed between normal and OS samples (P < 0.01) (excluding ATP6V1C2, whose protein expression did not differ significantly). Therefore, we identified 5 gene signatures that may be potential biomarkers for the detection and effective therapy of OS.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Osteossarcoma/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endonucleases Flap/genética , Endonucleases Flap/metabolismo , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Osteossarcoma/diagnóstico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Mapeamento de Interação de Proteínas , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , ATPases Vacuolares Próton-Translocadoras/genética , ATPases Vacuolares Próton-Translocadoras/metabolismoRESUMO
In the present study, the tissue-specific and temporal gene expression profiles of four catalogues of gonadal development-related genes (sex differentiation-related, steroid receptor, steroidogenic, and structural genes) were detected in nine tissues and during 11 successive developmental stages in the Pengze crucian carp (Pcc) (a triploid mono-female gynogenic fish). The results showed that these target genes exhibited overlapping distributions in various tissues, with the exception of Pcc-vasa and Pcc-cyp17a1. Gene expression profiling of the developmental stages showed that all of the target genes simultaneously reached peak expression levels at 40 and 48 days post hatching (dph). Both 40 and 48 dph appeared to be two key time points associated with the process of Pcc gonadal development. These data will provide a clear understanding of gene expression patterns associated with the gonadal development-related genes of this gynogenic teleost.
Assuntos
Carpas/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Animais , Carpas/crescimento & desenvolvimento , Carpas/metabolismo , Feminino , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Gônadas/crescimento & desenvolvimento , Gônadas/metabolismo , Masculino , Especificidade de ÓrgãosRESUMO
The aim of this study was to investigate the expression level of microRNA-499 and its clinical significance in serum of patients with acute myocardial infarction (AMI). We recruited 59 patients with AMI and 60 healthy individuals undergoing physical examination in our hospital during the same period as controls. Peripheral blood was drawn in the morning on the same day of microRNA extraction. The expression level of microRNA-499 was analyzed by real-time fluorescent quantitative polymerase chain reaction (qPCR). The sensitivity and specificity of the clinical diagnosis of AMI were analyzed by a receiver operating characteristic (ROC) curve. Fluorescent qPCR analysis showed that the expression of microRNA-499 in serum of patients with AMI was significantly higher than in controls (P < 0.05). MicroRNA-499 was detected in blood serum 3 h post-AMI, reaching a peak after 12 h and declining after 15 h. The area under the ROC curve (AUC) for the gold standard cardiac troponin I (cTnI) was 0.971 [95% confidence interval (CI): 0.951-1.000], and for the microRNA-499, AUC = 0.915 (95%CI: 0.826-1.000). When the microRNA-499 levels in patient and control (> 1.5) sera were compared, the sensitivity of microRNA-499 in judging AMI was found to be 86.37% and the specificity was 93.47%. Our results demonstrated that the expression levels of microRNA-499 in serum of patients with AMI were abnormal. Its high sensitivity and specificity for the diagnosis of AMI suggest that it would be useful as an auxiliary index for clinical diagnosis of AMI.