RESUMO
BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by severe loss of pancreatic ß cells. Immune cells are key mediators of ß cell destruction. This study attempted to investigate the role of immune cells and immune-related genes in the occurrence and development of T1DM. METHODS: The raw gene expression profile of the samples from 12 T1DM patients and 10 normal controls was obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by Limma package in R. The least absolute shrinkage and selection operator (LASSO)-support vector machines (SVM) were used to screen the hub genes. CIBERSORT algorithm was used to identify the different immune cells in distribution between T1DM and normal samples. Correlation of the hub genes and immune cells was analyzed by Spearman, and gene-GO-BP and gene-pathway interaction networks were constructed by Cytoscape plug-in ClueGO. Receiver operating characteristic (ROC) curves were used to assess diagnostic value of genes in T1DM. RESULTS: The 50 immune-related DEGs were obtained between the T1DM and normal samples. Then, the 50 immune-related DEGs were further screened to obtain the 5 hub genes. CIBERSORT analysis revealed that the distribution of plasma cells, resting mast cells, resting NK cells and neutrophils had significant difference between T1DM and normal samples. Natural cytotoxicity triggering receptor 3 (NCR3) was significantly related to the activated NK cells, M0 macrophages, monocytes, resting NK cells, and resting memory CD4+ T cells. Moreover, tumor necrosis factor (TNF) was significantly associated with naive B cell and naive CD4+ T cell. NCR3 [Area under curve (AUC) = 0.918] possessed a higher accuracy than TNF (AUC = 0.763) in diagnosis of T1DM. CONCLUSIONS: The immune-related genes (NCR3 and TNF) and immune cells (NK cells) may play a vital regulatory role in the occurrence and development of T1DM, which possibly provide new ideas and potential targets for the immunotherapy of diabetes mellitus (DM).
Assuntos
Diabetes Mellitus Tipo 1 , Área Sob a Curva , Diabetes Mellitus Tipo 1/genética , Redes Reguladoras de Genes , Humanos , Curva ROC , TranscriptomaRESUMO
Background: Numerous studies, ranging from the alleviation of tissue ischemia to the assessment of cancer prognosis, have demonstrated the fundamental biological differences between human umbilical cord blood-derived endothelial progenitor cells (CB-EPCs) and adult peripheral blood-derived endothelial progenitor cells (PB-EPCs). However, the underlying molecular mechanisms that produce these differences are not clear.The purpose of this study was to identify potential hub genes, key protein interactive networks, and correlated signal pathways unique to CB-EPC biology via bioinformatic methods. Materials and Methods: We selected the microarray dataset GSE39763 and identified the differentially expressed genes (DEGs) using the "limma" package in the RStudio software. These DEGs were annotated by gene ontology enrichment analyses and signal pathway analyses. A protein-protein interaction (PPI) analysis was then performed to construct PPI networks and identify a hub protein module. We further validated candidate DEGs from the selected module in the gene expression profiling interactive analysis (GEPIA) database because the DEGs were enriched in cancer pathways. Results: Setting an adjusted p-value <0.01 and |Log2 fold change (FC)| ≥ 2 as cutoff criteria, a total of 346 DEGs, including 314 upregulated genes and 32 downregulated genes in CB-EPCs, were identified. Expression of the genes encoding the AT-Hook Containing Transcription Factor 1 (AHCTF1), the Cancer Susceptibility Candidate 5 (CASC5), the Centromere Protein C (CENPC), the Centromere Protein E (CENPE), the Centromere Protein F (CENPF), the NUF2 Component of NDC80 Kinetochore Complex (NUF2), the RAN-Binding Protein 2 (RANBP2), the Shugoshin-like 2 (SGOL2), the Structural Maintenance of Chromosomes 3 (SMC3), and the Spindle Apparatus Coiled-Coil Protein 1 (SPDL1) proteins were specifically associated with CB-EPCs. Except for CENPC, the other nine genes' expression are all associated with a poorer overall survival rate in cancers. The expression levels of the CENPF and NUF2 genes in tumor patients were significantly higher than those in the controls. Conclusion: The CB-EPCs express genes with greater potential for proliferation and increased migration compared to PB-EPCs; in this regard they are similar to cancer cells.
Assuntos
Células Progenitoras Endoteliais/metabolismo , Sangue Fetal/metabolismo , Células-Tronco Mesenquimais/metabolismo , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Sangue Fetal/química , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Análise em Microsséries , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética , Transcriptoma/genética , Geleia de Wharton/citologiaRESUMO
PURPOSE: To examine the expression of RAD51 in oral squamous cell carcinoma (OSCC) and analyze its connection with pathological grade, clinical stage, and lymphatic metastasis potential. METHODS: For this study, 74 OSCC samples, 15 normal mucosa tissues, and 11 normal skin tissue samples were collected. RAD51 expression was investigated using immunohistochemistry. A follow-up visit was used to assess the prognosis of each patient. We compared RAD51 expression in oral mucosa epithelial cells (OMECs), keratinocytes, and tongue squamous cell carcinoma cells (TSCCs) by Western blot analysis. RESULTS: RAD51 expression was higher in tumor cells than in normal mucosal tissues. In addition, RAD51 expression was associated with higher tumor differentiation (P < 0.05). Also, RAD51 expression was higher (P < 0.05). Also, RAD51 expression was higher (P < 0.05). Also, RAD51 expression was higher (. CONCLUSION: A strong positive correlation was found between RAD51 expression and the degree of malignancy in OSCC patients, suggesting that RAD51 could be an excellent prognostic indicator for OSCC patients.