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Errores Innatos del Metabolismo de los Carbohidratos , Duplicación de Gen , Transportador de Glucosa de Tipo 1 , Humanos , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/deficiencia , Errores Innatos del Metabolismo de los Carbohidratos/genética , Masculino , Mutación , Femenino , Proteínas de Transporte de Monosacáridos/genética , Proteínas de Transporte de Monosacáridos/deficienciaRESUMEN
BACKGROUND: Hemoglobin (Hb) Hekinan II (A27; Glu-Asp) is an α-chain variant, and its interaction with the common Southeast Asian (--SEA/) α-thalassemia (α-thal) deletion is rarely reported. This study provides a clinical update of Hb Hekinan II associated with (--SEA/) α-thal. METHODS: A total of 11 simple heterozygotes and 20 composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal were included based on molecular diagnosis. RESULTS: Hb Hekinan II exhibited a significant increase in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin content, but a decrease in red blood cell level compared with α+ thalassemia deletion. Compared with (--SEA/) α-thal, composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal showed similar erythrocyte parameters. Both heterozygotes with and without (--SEA/) α-thal showed low Hb A2 level. Hb Hekinan II showed abnormal performance in high-performance liquid chromatography but not in capillary electrophoresis. CONCLUSION: Hb Hekinan II is a benign Hb variant. The heterozygotes exhibit clinically asymptomatic coinheritance with (--SEA/) α-thal having comparable hematological phenotype to simple (--SEA/) α-thal. The combination of hematological and molecular analysis helped to improve the detection rate of this rare variant.
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In area where α-thalassemia and ß-thalassemia are prevalent, the coinheritance of hemoglobin H disease (Hb H disease) and ß-thalassemia are not uncommon and could result in complex thalassemia intermedia syndromes. In this study, we investigate the hematological and molecular characteristics of two previously undescribed cases that co-inherited Hb H disease and rare ß-globin gene (HBB) mutations found in Chinese populations. Proband I was a boy with Hb H disease in association with IVS-II-5(G > C) (HBB:c0.315 + 5G > C) mutation. Proband II was a boy with a combination of Hb H and Hb Zengcheng [ß114(G16) Leu > Met; HBB:c.343C > A]. Both of them had mild hypochromic microcytic anemia, and neither had ever received a blood transfusion. In both cases, the level of Hb A2 was within normal range, and no Hb H was detected, but a small amount of Hb Bart's was observed in proband I. Routine DNA analysis detected the deletional Hb H disease in both cases. IVS-II-5(G > C) (HBB:c0.315 + 5G > C) and Hb Zengcheng (HBB:c.343C > A) mutations were found by DNA sequencing of ß-globin gene. The co-inheritance of Hb H disease with rare ß-thalassemia may result in an atypical pattern of Hb H disease, and further investigation of rare genotypes should be conducted to avoid missed diagnosis.
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Talasemia alfa , Talasemia beta , Humanos , Talasemia alfa/diagnóstico , Talasemia alfa/genética , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genética , Mutación , Fenotipo , GenotipoRESUMEN
BACKGROUND: A typical cancerous growth in the urinary tract, bladder cancer (BLCA) has a dismal survival rate and a poor chance of being cured. The cytoskeleton has been shown to be tightly related to tumor invasion and metastasis. Nevertheless, the expression of genes associated with the cytoskeleton and their prognostic significance in BLCA remain unknown. METHODS: In our study, we performed differential expression analysis of cytoskeleton-related genes between BLCA versus normal bladder tissues. According to the outcomes of this analysis of differentially expressed genes, all BLCA cases doing nonnegative matrix decomposition clustering analysis be classified into different molecular subtypes and were subjected to Immune cell infiltration analysis. We then constructed a cytoskeleton-associated gene prediction model for BLCA, and performed risk score independent prognostic analysis and receiver operating characteristic curve analyses to evaluate and validate the prognostic value of the model. Furthermore, enrichment analysis, clinical correlation analysis of prognostic models, and immune cell correlation analysis were carried out. RESULTS: We identified 546 differentially expressed genes that are linked to the cytoskeleton, including 314 up-regulated genes and 232 down-regulated genes. All BLCA cases doing nonnegative matrix decomposition clustering analysis could be classified into 2 molecular subtypes, and we observed differences (Pâ <â .05) in C1 and C2 immune scores about 9 cell types. Next, we obtained 129 significantly expressed cytoskeleton-related genes. A final optimized model was constructed consisting of 11 cytoskeleton-related genes. Survival curves and risk assessment predicted the prognostic risk in both groups of patients with BLCA. Survival curves and receiver operating characteristic curves were used to evaluate and validate the prognostic value of the model. Significant enrichment pathways for cytoskeleton-associated genes in bladder cancer samples were explored by Gene set enrichment analysis enrichment analysis. After we obtained the risk scores, a clinical correlation analysis was performed to examine which clinical traits were related to the risk scores. Finally, we demonstrated a correlation between different immune cells. CONCLUSION: Cytoskeleton-related genes have an important predictive value for BLCA, and the prognostic model we constructed may enable personalized treatment of BLCA.
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Neoplasias de la Vejiga Urinaria , Humanos , Pronóstico , Neoplasias de la Vejiga Urinaria/genética , Vejiga Urinaria , Citoesqueleto/genética , Análisis por ConglomeradosRESUMEN
Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Despite recent tremen-dous progress in managing CLL, the disease remains incurable with clinical therapies, and relapse is inevitable. To overcome this, new diagnostic and prognostic markers need to be investigated. We thus screened through the public database for genes with diagnostic, prognostic, and therapeutic implications in CLL. We further performed RT-qPCR and Western blot analysis to measure the candidate gene and protein expression levels, respectively, in peripheral blood mononuclear cells. Our results indicated that Glyoxalase 1 (GLO1) expression was significantly higher in patients with CLL than in healthy controls. Furthermore, cell proliferation, apoptosis, and cell cycle assay results together indicated that S-p-bromobenzylglutathione cyclopentyl diester (BBGC), an effective inhibitor of GLO1, suppresses the progression of CLL. Bioinformatics analysis revealed that GLO1 expression is closely associated with CDK4 expression in a wide variety of cancer types, and inhibition of CDK4 through silencing of genes or inhibitors can downregulate GLO1 expression. Subsequent validation experiments demonstrated that GLO1 protein levels were downregulated in MEC-1 and Jurkat cell lines after palbociclib exposure, and combination treatment of palbociclib with GLO1 inhibitor BBGC effectively delayed the growth of tumor cell lines.
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Leucemia Linfocítica Crónica de Células B , Humanos , Leucocitos Mononucleares , Piridinas/farmacología , Piperazinas/farmacología , ApoptosisRESUMEN
RATIONALE: Congenital factor VII deficiency is the most common among rare bleeding disorders, characterized by spontaneous or traumatic bleeding. The clinical manifestation is heterogeneous, ranging from asymptomatic phenotype to life-threatening hemorrhages. Intracranial hemorrhage is a common complication of brain tumor neurosurgery, which significantly challenges the perioperative management of patients with hemostatic defects. PATIENT CONCERNS: This report presented a 55-year-old man with congenital factor VII deficiency, who had no history of hemorrhage or family history. He underwent a craniotomy for the treatment of papillary craniopharyngioma. DIAGNOSES: The patient was diagnosed as papillary craniopharyngioma, factor VII deficiency, and atrial fibrillation. INTERVENTIONS: To prevent bleeding, a total of 8 doses of recombinant activated factor VII and 1 dose of fresh frozen plasma were administered as the perioperative replacement therapy. This scheme was guided by a pharmacodynamic evaluation, laboratory tests, and imaging examinations. OUTCOMES: No excessive surgical bleeding was observed during the 22-day treatment. The patient was found to have compound heterozygous mutations, Ala304Thr (c.910G > A) and IVS5-2A > G (c.572-2A > G), in the F7 gene. LESSONS: This is the first reported case in which surgical hemorrhage secondary to brain tumor resection was successfully controlled in the presence of congenital factor VII deficiency. Perioperative coagulation state, hemostasis, and thrombosis events should be closely observed, and the interval and dosage of recombinant factor VIIa should be adjusted accordingly.
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Neoplasias Encefálicas , Craneofaringioma , Deficiencia del Factor VII , Neurocirugia , Neoplasias Hipofisarias , Masculino , Humanos , Persona de Mediana Edad , Factor VIIa/uso terapéutico , Deficiencia del Factor VII/diagnóstico , Craneofaringioma/complicaciones , Proteínas Recombinantes/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Hipofisarias/complicaciones , Plasma , Factor VII/genética , Factor VII/uso terapéuticoRESUMEN
This study aimed to identify potential essential genes and pathways in diabetes of the exocrine pancreas (DEP) and explore possible molecular mechanisms. The array dataset GSE76895 was downloaded from the Gene Expression Omnibus database. Pancreatic tissue samples from 20 Diabetes of the exocrine pancreas and 32 nondiabetic individuals were selected for analysis. GEO2R analyzed differentially expressed genes (DEGs) in the 2 groups. Gene ontology annotation, Kyoto Encyclopedia of Genes Genomes and Reactome pathway enrichment analyses and Gene Set Enrichment Analysis were performed in this study. Protein-protein interaction (PPI) networks were constructed using Cytoscape software, and core networks were identified using MCODE plugins. A total of 62 genes, including 59 up-regulated and 3 down-regulated genes, were differentially expressed in DEP samples compared with nondiabetic patients. PPI network with 53 nodes and 138 edges was established. HLA-DRA is identified as the central gene of the PPI network and maybe a marker gene for DEP. Furthermore, up-regulated DEGs are mainly enriched in pathways related to the immune system and infection. The results of this study suggest that HLA-DRA and immune system pathways may play essential roles in DEP.
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Diabetes Mellitus , Páncreas Exocrino , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Ontología de Genes , Redes Reguladoras de Genes , Cadenas alfa de HLA-DR/genética , Humanos , Mapas de Interacción de Proteínas/genéticaRESUMEN
[This corrects the article DOI: 10.1155/2020/1970936.].
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SDF2L1 is a new type of endoplasmic reticulum stress inducible protein, which is related to poor prognosis of various cancer, we initially studied the low expression level of SDF2L1 in NPC, but the molecular mechanism of SDF2L1 in NPC needs further elucidation. To identify phosphorylated proteins regulated by SDF2L1 in nasopharyngeal carcinoma (NPC), Label-free Quantitative (LFQ) Proteomics and 2D-LC-MS/MS analysis were performed on high metastatic NPC 5-8F cells with overexpression of SDF2L1 and empty segment. Western blotting was applied to validate the differentially expressed phosphorylated proteins (DEPPs). As a result, 331 DEPPs were identified by proteomics, and PARVA phosphorylation (ser8) was validated. The present results suggested that PARVA phosphorylation may be a new promising biomarker for predicting NPC and play a key role in the occurrence and development of NPC.
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The function of tubulin polymerization promoting protein family member 3 (TPPP3) in tumor cells is complicated, and the role of TPPP3 in nasopharyngeal carcinoma (NPC) remains unclear. This study aims to explore the expression of TPPP3 in NPC and its effect on NPC cells. The expression of TPPP3 in NPC tissues and other cancers were analyzed by using the Oncomine and Gene Expression Omnibus (GEO) databases. The mRNA and protein of TPPP3 were detected in NPC tissues by quantitative real-time PCR and immunohistochemistry. Furthermore, TPPP3 was overexpressed in 5-8 F and HONE1 cell lines by lentivirus transfection, and functional analysis of TPPP3 in NPC was evaluated through in vitro experiments. The expression of TPPP3 was significantly down-regulated in NPC tissues and cells. Overexpression of TPPP3 significantly inhibited proliferation of 5-8 F and HONE1 cells in vitro. In addition, overexpression of TPPP3 significantly attenuated the invasion ability of 5-8 F, HONE1 cells in vitro, but have no significant effect on migration ability. Furthermore, TPPP3 overexpression diminished the expression of MMP-2 and MMP-9 mRNA. By analyzing dataset GSE12452, it was interesting that TPPP3 high expression group mainly functioned in B cell receptor signaling pathway, cell cycle and DNA replication. In conclusion, our results suggest that TPPP3 may be considered as an antioncogene, which plays an important role in the occurrence and progression of NPC.Abbreviations: TPPP3: tubulin polymerization promoting protein family member 3; NPC: nasopharyngeal carcinoma; GEO: Gene Expression Omnibus; qRT-PCR: quantitative real-time PCR; GFP: green fluorescence protein; MOI, transfected multiplicity of infection; CCK-8: cell counting kit-8; OD: optical density; GSEA: gene set enrichment analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; MMP-2: matrix metalloproteinase-2; MMP-9: matrix metalloproteinase-9.
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Proliferación Celular/genética , Proteínas del Citoesqueleto/genética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Invasividad Neoplásica/genética , Adulto , Anciano , Línea Celular Tumoral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Nasofaringe/patología , Transcriptoma/genéticaRESUMEN
Although human/eukaryotic ribosomal protein L14 (RPL14/eL14) is known to be associated with a variety of cancers, its role in nasopharyngeal carcinoma (NPC) remains unclear. The aim of this study was to explore the impact of RPL14(eL14) in NPC. The results of quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemical staining revealed that the expression of RPL14(eL14) significantly reduced in NPC tissues and cells. Furthermore, the protein expression of RPL14(eL14) was linked to NPC-related clinical pathological features, including the T and N classification of Tumor Node Metastasis (TNM) staging (all p < 0.05). Cell counting kit-8 (CCK-8) assay and colony formation assay revealed that RPL14(eL14) overexpression repressed NPC cell proliferation. In cell cycle assay, RPL14(eL14) overexpression significantly blocked NPC cells in S phase. Overexpression of RPL14(eL14) repressed cell migration and invasion in NPC as shown by transwell assay and cell scratch healing assay. In addition, RPL14(eL14) was closely correlated with the expression of epithelial-mesenchymal transition (EMT) biomarkers, including E-cadherin, N-cadherin, and vimentin as detected by western blot. In conclusion, our results revealed that RPL14(eL14) may be considered as an antioncogene in NPC, which greatly suppresses cancer progression.
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Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Proteínas Ribosómicas/genética , Adulto , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Nasofaringe/metabolismo , Nasofaringe/patología , Proteínas Ribosómicas/metabolismo , Vimentina/genética , Vimentina/metabolismoRESUMEN
ß-Thalassemia (ß-thal) is a hereditary blood disorder characterized by the reduced or absent synthesis of ß-globin chains. Here, we report a case of severe thalassemia with compound heterozygosity for a novel deletion mutation at codon 104 (-A) (HBB: c.313delA) and codons 41/42 (-CTTT) (HBB: c.126_129delCTTT) on the ß-globin gene (HBB), and a coinheritance of the -α4.2 (leftward) deletion on the α-globin gene cluster. The proband was a 12-year-old boy, and four other family members were involved in this study. This novel frameshift mutation caused classical ß-thal trait in the heterozygote and a transfusion-dependent form of ß-thal major (ß-TM) in compound heterozygosity with other ß0 mutations.
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Pueblo Asiatico/genética , Codón , Heterocigoto , Mutación , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genética , Alelos , Sustitución de Aminoácidos , Niño , China , Análisis Mutacional de ADN , Índices de Eritrocitos , Exones , Femenino , Mutación del Sistema de Lectura , Humanos , Masculino , LinajeRESUMEN
The purpose of this study was to explore the relationship between stromal cell-derived factor 2-like 1 (SDF2L1) and nasopharyngeal carcinoma (NPC). 12 NPC tissues and 12 chronic nasopharyngitis tissues were involved in our study. Quantitative real-time PCR (qRT-PCR) and Western Blot were utilized to detect the expression of SDF2L1. Besides, immunofluorescence analysis was utilized to determine the protein expression of 97 paraffin-embedded NPC tissues and 58 nasopharyngitis tissues. Biological functional experiment included Cell Counting Kit-8 (CCK-8) assay, cell clone formation assay, cell scratch migration assay, Transwell migration assay, and Transwell invasion assay. All data were analyzed by SPSS. Results showed that downexpression of SDF2L1 was prominently present in NPC tissues and cells. Furthermore, silencing the expression of SDF2L1 promoted NPC proliferation, migration, and invasion in vitro, while overexpression of SDF2L1 has the opposite effect. In conclusion, SDF2L1 may act as a cancer suppressor gene, play a crucial role in the occurrence and development of NPC, and be a new therapeutic target or prognostic indicator for NPC.
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Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Nasofaringitis/genética , Adulto , Anciano , Movimiento Celular , Proliferación Celular , Enfermedad Crónica , Femenino , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Humanos , Lentivirus/genética , Lentivirus/metabolismo , Masculino , Proteínas de la Membrana/agonistas , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Nasofaringitis/metabolismo , Nasofaringitis/patología , Invasividad Neoplásica , TransfecciónRESUMEN
Tubulin polymerization promoting protein family member 3 (TPPP3) is a kind of protein that can mediate the dynamics and stability of microtubules. However, the correlations of TPPP3 between prognosis and immune infiltrates in different tumors are still unclear. The analysis of TPPP3 expression was performed via Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) website. We also used GEPIA to assess the impact of TPPPT3 on clinical outcomes. The related pathways involved in TPPP3 were analyzed by gene-set enrichment analysis (GSEA), and the correlation between TPPP3 and immune infiltration was studied by Tumor Immune Estimation Resource2.0 (TIMER 2.0). The TPPP3 expression was significantly reduced in head and neck squamous carcinoma (HNSC) compared to adjacent tissues. In addition, the low expression of TPPP3 in HNSC was significantly associated with prognosis. The pathways closely related to the low expression of TPPP3 are "Antigen Processing and Presentation," "Primary Immunodeficiency," and so on. The TPPP3 expression was negatively correlated with the level of CD8+ T cell, B cell, and myeloid dendritic cell infiltration in HNSC. The TPPP3 expression is closely related to multiple immunomarkers in CD8+ T cell and Myeloid dendritic cells. These data indicate that TPPP3 is associated with multiple cancers and involves multiple immune-related pathways, and TPPP3 is associated with immune infiltration levels. Besides, the TPPP3 expression may help regulate tumor-associated CD8 + T cells, DC cells in HNSC. We conclude TPPP3 can be considered as a biomarker for predicting head and neck squamous cell carcinoma prognosis and immune infiltration.
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Biomarcadores de Tumor/genética , Proteínas del Citoesqueleto/genética , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Adulto , Biomarcadores de Tumor/metabolismo , Proteínas del Citoesqueleto/metabolismo , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
OBJECTIVE: To explore the expression of immune-related lncRNAs in colon adenocarcinoma and find out the effect on how these lncRNAs influence the development and prognosis of colon adenocarcinoma. METHOD: Transcriptome data of colon adenocarcinoma from The Cancer Genome Atlas (TCGA) were downloaded, and gene sets "IMMUNE RESPONSE" and "IMMUNE SYSTEM PROCESS" were sought from the Molecular Signatures Database (MSigDB). The expression of immune-related genes was extracted that were immune-related mRNAs. Then, the immune-related lncRNAs were sought out by utilizing of the above data. Clinical traits were combined with immune-related lncRNAs, so that prognostic-related lncRNAs were identified by Cox regression. Multivariate Cox regression was built to calculate risk scores. Relationships between clinical traits and immune-related lncRNAs were also calculated. RESULT: A total of 480 colorectal adenocarcinoma patients and 41 normal control patients' transcriptome sequencing data of tissue samples were obtained from TCGA database. 918 immune-related lncRNAs were screened. Cox regression showed that 34 immune-related lncRNAs were associated with colon adenocarcinoma prognosis. Seven lncRNAs were independent risk factors. CONCLUSION: This study revealed that some lncRNAs can affect the development and prognosis of colon adenocarcinoma. It may provide new theory evidence of molecular mechanism for the future research and molecular targeted therapy of colon adenocarcinoma.
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Adenocarcinoma , Neoplasias del Colon , ARN Largo no Codificante/genética , Transcriptoma/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/mortalidad , Humanos , Pronóstico , ARN Largo no Codificante/análisisRESUMEN
BACKGROUND: The aim of this study is to identify possible prognostic-related immune genes in bladder urothelial carcinoma and to try to predict the prognosis of bladder urothelial carcinoma based on these genes. METHODS: The Cancer Genome Atlas (TCGA) expression profile data and corresponding clinical traits were obtained. Differential gene analysis was performed using R software. Reactome was used to analyze the pathway of immune gene participation. The differentially expressed transcription factors and differentially expressed immune-related genes were extracted from the obtained list of differentially expressed genes, and the transcription factor-immune gene network was constructed. To analyze the relationship between immune genes and clinical traits of bladder urothelial carcinoma, a multifactor Cox proportional hazards regression model based on the expression of immune genes was established and validated. RESULTS: Fifty-eight immune genes were identified to be associated with the prognosis of bladder urothelial carcinoma. These genes were enriched in Cytokine Signaling in Immune System, Signaling by Receptor Tyrosine Kinases, Interferon alpha/beta signaling, and other immune related pathways. Transcription factor-immune gene regulatory network was established, and EBF1, IRF4, SOX17, MEF2C, NFATC1, STAT1, ANXA6, SLIT2, and IGF1 were screened as hub genes in the network. The model calculated by the expression of 16 immune genes showed a good survival prediction ability (p < 0.05 and AUC = 0.778). CONCLUSION: A transcription factor-immune gene regulatory network related to the prognosis of bladder urothelial carcinoma was established. EBF1, IRF4, SOX17, MEF2C, NFATC1, STAT1, ANXA6, SLIT2, and IGF1 were identified as hub genes in the network. The proportional hazards regression model constructed by 16 immune genes shows a good predictive ability for the prognosis of bladder urothelial carcinoma.
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Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica/inmunología , Redes Reguladoras de Genes/inmunología , Proteínas de Neoplasias , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Perfilación de la Expresión Génica , Humanos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/inmunología , Pronóstico , Neoplasias de la Vejiga Urinaria/diagnósticoRESUMEN
BACKGROUND: Pheochromocytoma/paraganglioma (PCPG) is a benign neuroendocrine neoplasm in most cases, but metastasis and other malignant behaviors can be observed in this tumor. The aim of this study was to identify genes associated with the metastasis of PCPG. METHODS: The Cancer Genome Atlas (TCGA) expression profile data and clinical information were downloaded from the cbioportal, and the weighted gene coexpression network analysis (WGCNA) was conducted. The gene coexpression modules were extracted from the network through the WGCNA package of R software. We further extracted metastasis-related modules of PCPG. Enrichment analysis of Biological Process of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes was carried out for important modules, and survival analysis of hub genes in the modules was performed. RESULTS: A total of 168 PCPG samples were included in this study. The weighted gene coexpression network was constructed with 5125 genes of the top 25% variance among the 20501 genes obtained from the database. We identified 11 coexpression modules, among which the salmon module was associated with the age of PCPG patients at diagnosis, metastasis, and malignancy of the tumors. CONCLUSION: WGCNA was performed to identify the gene coexpression modules and hub genes in the metastasis-related gene module of PCPG. The findings in this study provide a new clue for further study of the mechanisms underlying the PCPG metastasis.
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Neoplasias de las Glándulas Suprarrenales/genética , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Paraganglioma/genética , Paraganglioma/patología , Feocromocitoma/genética , Feocromocitoma/patología , Ontología de Genes , Humanos , Metástasis de la Neoplasia , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To explore the molecular basis for a pedigree affected with May-Hegglin anomaly (MHA). METHODS: Peripheral blood samples were collected and subjected to DNA extraction. Exons 1, 10, 16, 24, 25, 26, 30, 31, 33, 38 and 40 and flanking sequences of the MYH9 gene were subjected to PCR amplification and Sanger sequencing. Changes in protein expression were determined by an indirect immunofluorescence assay. Platelet aggregation function of the proband was assessed by thromboelastogram. RESULTS: The proband and his second son both carried a heterozygous 5521G>A (GAG to AAG) missense variant in exon 38 of the MYH9 gene, leading to p.Glu1841Lys substitution at position 1841 of amino acid sequence. Immunofluorescence showed inclusions containing NMMHC-II A. Thromboelastogram suggested enhanced platelet aggregation function of the proband. CONCLUSION: The c.5521G>A variant of MYH9 gene has co-segregated with the phenotype of MHA in this pedigree. To assess the aggregation function of platelet by thromboelastogram can predict the risk of bleeding in MHA patients.
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Pérdida Auditiva Sensorineural , Cadenas Pesadas de Miosina , Trombocitopenia/congénito , Pérdida Auditiva Sensorineural/genética , Humanos , Masculino , Mutación , Cadenas Pesadas de Miosina/genética , Linaje , Trombocitopenia/genéticaRESUMEN
The role of autophagy in tumors is complex; based on known interactions between autophagy and hepatocellular carcinoma (HCC) pathogenesis, we hypothesized that autophagy-related genes (ARGs) may play an important role in HCC. The ARGs were obtained from the Human Autophagy Database and the Gene Set Enrichment Analysis. Based on the area under the curve (AUC) value >0.9 with p <0.0001 and Student's T-test analysis with p <0.0001, differently expressed autophagy-related genes (DEARGs) with high diagnostic efficiency were found. Besides that, we searched in the PubMed database to find novel DEARGs associated with HCC. Then the DEARGs were validated in the GSE25097, GSE54236, GSE76427, GSE64041, Oncomine, and Human Protein Atlas datasets. Finally, survival analysis of CHAF1B in HCC and correlations of clinico-pathological characteristics and CHAF1B were performed based on the TCGA database. The mRNA and protein expression of 531 ARGs were analyzed and validated in eight independent cohorts. First, 18 DEARGs with high diagnostic efficiency were selected from the TCGA database, and nine of them were identified that had not previously been associated with HCC. These nine DEARGs were validated in the GSE25097, GSE54236, GSE76427, GSE64041, Oncomine, and Human Protein Atlas datasets. Additionally, we found that CHAF1B was associated with overall survival and relapse free survival at one, three, and five years. Furthermore, the univariate and multivariate Cox analyses revealed that the high expression of CHAF1B was an independent risk factor in HCC patients. This research demonstrated that CHAF1B was a novel diagnostic and prognostic signature biomarker that could be potentially useful for predicting the development of HCC and may provide new insights for HCC tumorigenesis and treatments.
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OBJECTIVE: The purpose of our research was to demonstrate the clinical significance of serum bilirubin in primary Sjögren syndrome patients (pSS). PATIENTS AND METHODS: A total of 116 patients with primary Sjögren syndrome and 138 matched individuals were included in our study. The laboratory parameters of patients with pSS and healthy controls were retrospectively analyzed. RESULTS: Serum total bilirubin, direct bilirubin, and indirect bilirubin were significantly reduced (P < .001, P = .001, P < .001) while ESR was significantly increased (P < .001) in patients with pSS when compared with healthy checkup individuals. Statistically, the AUC in patients with pSS is as follows: TBIL = 0.77, P < .001, cutoff value = 7.96; DBIL = 0.617, P = .001 cutoff value = 2.2; and IBIL = 0.786, P < .001 cutoff value = 4.5. Furthermore, our study revealed that TBIL, DBIL, and IBIL were significantly negativity related to ESR (r = -.406, P < .001; r = -.206, P = .026; r = -.429, P < .001). Interestingly, multiple linear regression analysis showed that when adjusted for sex, age, ALT, and AST, the levels of TBIL, DBIL, and IBIL in patients with pSS were independently correlated with ESR. CONCLUSIONS: This study found that the levels of serum bilirubin were reduced and the inflammatory marker was elevated in patients with pSS. Additionally, serum bilirubin was negatively related with ESR and TBIL, DBIL, and IBIL can be used in the clinical diagnosis and follow-up visits of the patients with pSS.