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1.
Oral Dis ; 29(4): 1726-1737, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35119164

RESUMO

OBJECTIVE: This study aimed to profile differentially expressed (DE) exosomal RNAs in healthy subjects and periodontitis patients and compare their levels before and after treatment. MATERIALS AND METHODS: Plasma samples from healthy subjects and patients with periodontitis (pre-/post-periodontal treatment) were collected for this case-control study. After isolation of exosomes from the plasma, the RNA was extracted and small RNA sequencing was performed (3 healthy samples, 4 pre-treatment samples, and 5 post-treatment samples). Two-way analyses were conducted according to the treatment status in the periodontitis group, unpaired analysis (grouping as pre-/post-treatment) and paired analysis (matching pre- and post-treatment in the same subject). The DE exosomal RNAs were screened by sequencing and visualized using the R software. Gene Ontology analysis was performed, and target genes were identified. RESULTS: In both paired and unpaired analyses, two DE microRNAs (DEmiRs; miR-1304-3p and miR-200c-3p) and two DE small nucleolar RNAs (DEsnoRs; SNORD57 and SNODB1771) were common, and they were found to be downregulated during periodontitis and recovered to healthy levels after treatment. The top three target genes (NR3C1, GPR158, and CNN3) commonly regulated by DEmiRs were identified. CONCLUSIONS: Plasma-derived exosomal miRs (miR-1304-3p and miR-200c-3p) and snoRs (SNORD57 and SNODB1771) could be valuable biomarkers for periodontitis.


Assuntos
Exossomos , MicroRNAs , Periodontite , Humanos , Projetos Piloto , Estudos de Casos e Controles , MicroRNAs/genética , Biomarcadores/metabolismo , Exossomos/genética , Exossomos/metabolismo , Periodontite/genética , Periodontite/metabolismo , Perfilação da Expressão Gênica
2.
J Virol ; 95(6)2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33361419

RESUMO

Human papillomavirus (HPV) infects squamous epithelium and is a major cause of cervical cancer (CC) and a subset of head and neck cancers (HNC). Virus-induced tumorigenesis, molecular alterations, and related prognostic markers are expected to be similar between the two cancers, but they remain poorly understood. We present integrated molecular analysis of HPV-associated tumors from TCGA and GEO databases and identify prognostic biomarkers. Analysis of gene expression profiles identified common upregulated genes and pathways of DNA replication and repair in the HPV-associated tumors. We established 34 prognostic gene signatures with a universal cutoff value in TCGA-CC using Elastic Net Cox regression analysis. We were able to externally validate our results in the TCGA-HNC and several GEO data sets, and demonstrated prognostic power in HPV-associated HNC, but not in HPV-negative cancers. The HPV-related prognostic and predictive indicator did not discriminate other cancers, except bladder urothelial carcinoma. These results identify and completely validate a highly selective prognostic system and its cross-usefulness in HPV-associated cancers, regardless of the tumor's anatomical subsite.IMPORTANCE Persistent infection with high-risk HPV interferes with cell function regulation and causes cell mutations, which accumulate over the long term and eventually develop into cancer. Results of pathway enrichment analysis presumably showed this accumulation of intracellular damage during the chronic HPV-infected state. We used highly advanced statistical methods to identify the most appropriate genes and coefficients and developed the HPV-related prognostic and predictive indicator (HPPI) risk scoring system. We applied the same cutoff value to training and validation sets and demonstrated good prognostic performance in both data sets, and confirmed a consistent trend in external validation. Moreover, HPPI presented significant validation results for bladder cancer suspected to be related to HPV. This suggested that our risk scoring system based on the prognostic gene signature could play an important role in the development of treatment strategies for patients with HPV-related cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias/genética , Papillomaviridae/fisiologia , Infecções por Papillomavirus/genética , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Neoplasias/virologia , Infecções por Papillomavirus/virologia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
3.
Cancer Cell Int ; 22(1): 135, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35346218

RESUMO

BACKGROUND: Microbiome has been shown to substantially contribute to some cancers. However, the diagnostic implications of microbiome in head and neck squamous cell carcinoma (HNSCC) remain unknown. METHODS: To identify the molecular difference in the microbiome of oral and non-oral HNSCC, primary data was downloaded from the Kraken-TCGA dataset. The molecular differences in the microbiome of oral and non-oral HNSCC were identified using the linear discriminant analysis effect size method. RESULTS: In the study, the common microbiomes in oral and non-oral cancers were Fusobacterium, Leptotrichia, Selenomonas and Treponema and Clostridium and Pseudoalteromonas, respectively. We found unique microbial signatures that positively correlated with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in oral cancer and positively and negatively correlated KEGG pathways in non-oral cancer. In oral cancer, positively correlated genes were mostly found in prion diseases, Alzheimer disease, Parkinson disease, Salmonella infection, and Pathogenic Escherichia coli infection. In non-oral cancer, positively correlated genes showed Herpes simplex virus 1 infection and Spliceosome and negatively correlated genes showed results from PI3K-Akt signaling pathway, Focal adhesion, Regulation of actin cytoskeleton, ECM-receptor interaction and Dilated cardiomyopathy. CONCLUSIONS: These results could help in understanding the underlying biological mechanisms of the microbiome of oral and non-oral HNSCC. Microbiome-based oncology diagnostic tool warrants further exploration.

4.
J Toxicol Environ Health A ; 83(3): 126-134, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114955

RESUMO

Malignant pleural mesothelioma (MPM) is a type of cancer characterized by a short survival time and poor prognosis. Malignant pleural mesothelioma is most frequently associated with exposure to asbestos and other elongated mineral fibers. The aim of this study was to examine molecular differences between asbestos-exposed and non-exposed MPM patients and assess prognostic significances of molecular factors. Clinical and genetic data were downloaded from Cancer Genome Atlas. To identify the molecular differences, Significant Analysis of Microarray method was used. Prognostic significances of differentially expressed genes were confirmed by using Kaplan-Meier curve with the Log-Rank test. Although mRNAs did not exhibit any significant differences between the two patient groups, nine miRNAs were found to be down-regulated in the asbestos-exposed group. The top five pathways most relevant to the selected miRNAs were extracted through pathway enrichment analysis. Survival analysis revealed that high expression of only hsa-miR-98 was significantly associated with poor prognosis in patients with asbestos-exposed MPM. Evidence suggests that management of the aggressiveness and progression of asbestos-induced MPM may require high levels of hsa-miR-98 due to its tumor-suppressive role. This study might be helpful in enhancing our understanding of the biological mechanisms underlying asbestos-induced MPM and for acquiring greater insights into targeted therapy.Abbreviations: FDR: false discovery rate; MM: malignant mesothelioma; MPM: malignant pleural mesothelioma; mRNA: messenger RNA; miRNA: microRNA; SAM: significance analysis of microarrays; TCGA: the cancer genome atlas.


Assuntos
Amianto/toxicidade , Carcinógenos/toxicidade , Mesotelioma/diagnóstico , MicroRNAs/metabolismo , Idoso , Biomarcadores Tumorais , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Mesotelioma/induzido quimicamente , MicroRNAs/genética , Pessoa de Meia-Idade
5.
J Med Internet Res ; 22(5): e16084, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369034

RESUMO

BACKGROUND: Prognostic genes or gene signatures have been widely used to predict patient survival and aid in making decisions pertaining to therapeutic actions. Although some web-based survival analysis tools have been developed, they have several limitations. OBJECTIVE: Taking these limitations into account, we developed ESurv (Easy, Effective, and Excellent Survival analysis tool), a web-based tool that can perform advanced survival analyses using user-derived data or data from The Cancer Genome Atlas (TCGA). Users can conduct univariate analyses and grouped variable selections using multiomics data from TCGA. METHODS: We used R to code survival analyses based on multiomics data from TCGA. To perform these analyses, we excluded patients and genes that had insufficient information. Clinical variables were classified as 0 and 1 when there were two categories (for example, chemotherapy: no or yes), and dummy variables were used where features had 3 or more outcomes (for example, with respect to laterality: right, left, or bilateral). RESULTS: Through univariate analyses, ESurv can identify the prognostic significance for single genes using the survival curve (median or optimal cutoff), area under the curve (AUC) with C statistics, and receiver operating characteristics (ROC). Users can obtain prognostic variable signatures based on multiomics data from clinical variables or grouped variable selections (lasso, elastic net regularization, and network-regularized high-dimensional Cox-regression) and select the same outputs as above. In addition, users can create custom gene signatures for specific cancers using various genes of interest. One of the most important functions of ESurv is that users can perform all survival analyses using their own data. CONCLUSIONS: Using advanced statistical techniques suitable for high-dimensional data, including genetic data, and integrated survival analysis, ESurv overcomes the limitations of previous web-based tools and will help biomedical researchers easily perform complex survival analyses.


Assuntos
Neoplasias/genética , Análise de Sobrevida , Humanos , Internet , Neoplasias/mortalidade , Prognóstico
6.
Int J Mol Sci ; 21(9)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32354205

RESUMO

Relapse of acute lymphoblastic leukemia (ALL) is dangerous and it worsens the prognosis of patients; however, prognostic markers or therapeutic targets for ALL remain unknown. In the present study, using databases such as TARGET, GSE60926 and GSE28460, we determined that KIF2C and its binding partner, KIF18B are overexpressed in patients with relapsed ALL compared to that in patients diagnosed with ALL for the first time. As 50% of the residues are exactly the same and the signature domain of KIF2C is highly conserved between human and zebrafish, we used zebrafish embryos as a model to investigate the function of kif2c in vivo. We determined that kif2c is necessary for lymphopoiesis in zebrafish embryos. Additionally, we observed that kif2c is not related to differentiation of HSCs; however, it is important for the maintenance of HSCs as it provides survival signals to HSCs. These results imply that the ALL relapse-related gene KIF2C is linked to the survival of HSCs. In conclusion, we suggest that KIF2C can serve as a novel therapeutic target for relapsed ALL.


Assuntos
Cinesinas/genética , Recidiva Local de Neoplasia/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Peixe-Zebra/embriologia , Sequência de Aminoácidos , Animais , Biomarcadores Tumorais/genética , Sequência Conservada , Bases de Dados Genéticas , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Regulação Neoplásica da Expressão Gênica , Hematopoese , Humanos , Cinesinas/química , Masculino , Domínios Proteicos , Regulação para Cima , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
7.
ACS Appl Mater Interfaces ; 16(12): 14583-14594, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38478505

RESUMO

Healing chronic diabetic wounds is challenging because of excessive reactive oxygen species (ROS) and hypoxia in the wound microenvironment. To address this issue, we propose a hydrogel wound dressing composed of polyethylene glycol (PEG) cross-linked with a biomimetic catalase, Fe-containing porphyrin (FeP) (i.e., FeP hydrogel). The immobilized FeP can serve as a catalyst for both ROS scavenging and O2 generation. The properties of the hydrogels were optimized by varying the composition ratios of the two constituent materials based on their mechanical properties and catalytic activity. Our in vitro cell experiments revealed that the FeP-80 hydrogel enhanced the proliferation and migration of keratinocytes and dermal fibroblasts and promoted the expression of angiogenic growth factors in keratinocytes. When tested with an in vivo diabetic chronic wound model, the FeP-80 hydrogel promoted wound healing by facilitating re-epithelialization, promoting angiogenesis, and suppressing inflammation, compared with other control groups.


Assuntos
Diabetes Mellitus , Hidrogéis , Humanos , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Oxigênio , Cicatrização , Antibacterianos
8.
J Clin Monit Comput ; 27(5): 535-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23529343

RESUMO

Esophageal stethoscope is less invasive and easy to handling. And it gives a lot of information. The purpose of this study is to investigate the correlation of blood pressure and heart sound as measured by esophageal stethoscope. Four male beagles weighing 10 to 12 kg were selected as experimental subjects. After general anesthesia, the esophageal stethoscope was inserted. After connecting the microphone, the heart sounds were visualized and recorded through a self-developed equipment and program. The amplitudes of S1 and S2 were monitored real-time to examine changes as the blood pressure increased and decreased. The relationship between the ratios of S1 to S2 (S1/S2) and changes in blood pressure due to ephedrine was evaluated. The same experiment was performed with different concentration of isoflurane. From S1 and S2 in the inotropics experiment, a high correlation appeared with change in blood pressure in S1. The relationship between S1/S2 and change in blood pressure showed a positive correlation in each experimental subject. In the volatile anesthetics experiment, the heart sounds decreased as MAC increased. Heart sounds were analyzed successfully with the esophageal stethoscope through the self-developed program and equipment. A proportional change in heart sounds was confirmed when blood pressure was changed using inotropics or volatile anesthetics. The esophageal stethoscope can achieve the closest proximity to the heart to hear sounds in a non-invasive manner.


Assuntos
Diagnóstico por Computador/instrumentação , Esôfago/fisiologia , Auscultação Cardíaca/instrumentação , Ruídos Cardíacos/fisiologia , Processamento de Sinais Assistido por Computador/instrumentação , Espectrografia do Som/instrumentação , Estetoscópios , Animais , Pressão Sanguínea/fisiologia , Cães , Desenho de Equipamento , Análise de Falha de Equipamento , Auscultação Cardíaca/métodos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrografia do Som/métodos
9.
Int Immunopharmacol ; 120: 110286, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37216801

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage and bone damage. Exosomes are small extracellular vesicles that play a critical role in intercellular communication and various biological processes by serving as vehicles for the transfer of diverse molecules, such as nucleic acids, proteins, and lipids, between cells. The purpose of this study was to develop potential biomarkers for RA in peripheral blood by performing small non-coding RNA (sncRNA) sequencing using circulating exosomes from healthy controls and patients with RA. METHODS: In this study, we investigated extracellular sncRNAs associated with RA in peripheral blood. Using RNA sequencing and differentially expressed sncRNA analysis, we identified a miRNA signature and target genes. Target gene expression was validated via the four GEO datasets. RESULTS: Exosomal RNAs were successfully isolated from the peripheral blood of 13 patients with RA and 10 healthy controls. The hsa-miR-335-5p and hsa-miR-486-5p expression levels were higher in patients with RA than in controls. We identified the SRSF4 gene, which is a common target of hsa-miR-335-5p and hsa-miR-483-5p. As expected, the expression of this gene was found to be decreased in the synovial tissues of patients with RA through external validation. In addition, hsa-miR-335-5p was positively correlated with antiCCP, DAS28ESR, DAS28CRP, and rheumatoid factor. CONCLUSIONS: Our results provide strong evidence that circulating exosomal miRNA (hsa-miR-335-5p and hsa-miR-486-5p) and SRSF4 could be valuable biomarkers for RA.


Assuntos
Artrite Reumatoide , MicroRNAs , Humanos , MicroRNAs/metabolismo , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Biomarcadores
10.
Front Biosci (Landmark Ed) ; 27(1): 2, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-35090306

RESUMO

BACKGROUND: Human papillomavirus (HPV) is the major cause of cervical cancer (CC) etiology; its contribution to head and neck cancer (HNC) incidence is steadily increasing. As individual patients' response to the treatment of HPV-associated cancer is variable, there is a pressing need for the identification of biomarkers for risk stratification that can help determine the intensity of treatment. METHODS: We have previously reported a novel prognostic and predictive indicator (HPPI) scoring system in HPV-associated cancers regardless of anatomical location by analyzing The Cancer Genome Atlas and Gene Expression Omnibus databases. In the present study, we comprehensively investigated the association of group-specific expression patterns of common differentially expressed genes (DEGs) between high- and low-risk groups in HPV-associated CC and HNC, identifying molecular biomarkers and pathways for risk stratification. RESULTS: Among the 174 identified DEGs, the expression of genes associated with extracellular matrix (ECM)-receptor interaction pathway (ITGA5, ITGB1, LAMB1, and LAMC1) was increased in high-risk groups in both HPV-associated CC and HNC, while the expression of genes associated with T-cell immunity (CD3D, CD3E, CD8B, LCK, and ZAP70) was decreased and vice versa. The individual genes showed significant prognostic impact on HPV-associated cancers but not on HPV-negative cancers. The expression levels of identified genes were similar between HPV-negative and HPV-associated high-risk groups with distinct expression patterns only in HPV-associated low-risk groups. Each group of genes showed negative correlations and distinct patterns of immune cell infiltration in tumor microenvironments. CONCLUSIONS: These results allowed us to identify molecular biomarkers and pathways for risk stratification in HPV-associated cancers regardless of anatomical location. The identified targets were found to be selectively working in only HPV-associated cancers and not in HPV-negative cancers, indicating the possibility of selective targets governing HPV-infective tumor microenvironments.


Assuntos
Alphapapillomavirus , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Feminino , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Medição de Risco , Microambiente Tumoral
11.
Ann Clin Lab Sci ; 52(3): 494-498, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35777808

RESUMO

Autosomal dominant hypocalcemia (ADH) is characterized by hypocalcemia and inappropriately low PTH concentrations. ADH type 2 (ADH2) is caused by a heterozygous gain-of-function mutation in GNA11 that encodes the subunit of G11, the principal G protein that transduces calcium-sensing receptor signaling in the parathyroid. Clinical features related to hypocalcemia in ADH2 range from asymptomatic to tetany and seizures. We report the clinical and molecular analysis of an infant with ADH2. Exome sequencing identified a de novo heterozygous missense variant, c. G548C (p. Arg183Pro) in GNA11. This is the youngest Korean case to be diagnosed with ADH 2. In addition, we summarized the literature related to eight mutations in GNA11 from 10 families.


Assuntos
Subunidades alfa de Proteínas de Ligação ao GTP , Hipocalcemia , Hipoparatireoidismo , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Humanos , Hipercalciúria/genética , Hipercalciúria/metabolismo , Hipocalcemia/diagnóstico , Hipocalcemia/genética , Hipocalcemia/metabolismo , Hipoparatireoidismo/congênito , Hipoparatireoidismo/genética , Hipoparatireoidismo/metabolismo , Lactente
12.
Biosci Biotechnol Biochem ; 75(10): 2018-20, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21979078

RESUMO

Two novel non-synonymous SNPs in the 2nd and 3rd exons of the porcine ApoR gene are reported. One was identified as a novel SNP significantly associated with multiple traits of pork meat quality. The data can provide a useful resource for developing a marker in the genetic improvement of pigs.


Assuntos
Apolipoproteínas/genética , Carne , Polimorfismo de Nucleotídeo Único/genética , Suínos , Animais , Éxons/genética , Lipoproteínas VLDL/química , Controle de Qualidade
13.
Artigo em Inglês | MEDLINE | ID: mdl-34070783

RESUMO

To manage depression of older men, it is necessary to identify factors that influence depression and improve them. This study used the Korean Aging Longitude Research to understand the effects of labor exclusion and relationship exclusion on depression in Korean male seniors aged 65 and older. According to research on the effect of labor exclusion and relationship exclusion on depression, depression in the case where labor was excluded was 1.69 times higher in 2014, 1.65 times higher in 2016, and 1.93 times higher in 2018 compared to the case where labor was not excluded. Depression in the case where relationship was excluded was 2.94 times higher in 2014, 3.15 times higher in 2016, and 2.57 times higher in 2018 compared to the case where relationship was not excluded. Depression in the case where labor and relationship were both excluded was 3.00 times higher in 2014, 3.23 times higher in 2016, and 2.81 times higher in 2018 compared to the case where neither labor nor relationship was excluded. Since labor exclusion and relationship exclusion have a big influence on depression in older men, it is necessary to establish plans for job creation and for the formation of social relationships for the elderly.


Assuntos
Envelhecimento , Idoso , Humanos , Masculino , República da Coreia/epidemiologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-34444113

RESUMO

(1) Background: Korea operates its national health insurance (NHI) system as a form of public health insurance, and is commonly regarded as having achieved universal health coverage (UHC). However, many Korean households register for additional private health insurance (PHI) programs. Typically, registration rates for PHI are higher for individuals with a higher socioeconomic status (SES). A difference in mortality between those with and without additional PHI would indicate that there are health inequalities within the Korean NHI system under UHC. Therefore, this study aimed to confirm whether additional PHI affects mortality under the Korean NHI system. (2) Methods: We conducted a longitudinal study using the Korean Longitudinal Study of Aging data from the first to the sixth wave. The analysis included 8743 participants, who were divided into two groups: those who only had NHI and those who had both NHI and PHI. Differences in mortality between the two groups were compared using the Cox proportional hazard regression. (3) Results: The group with both NHI and PHI had lower mortality than the group with only NHI (hazard ratio = 0.53, 95% confidence interval: 0.41, 0.9). (4) Conclusions: The results of this study reveal that there are health disparities according to SES and PHI within the Korean NHI system under UHC. Therefore, relevant government institutions and experts should further improve the NHI system to reduce health disparities.


Assuntos
Seguro Saúde , Cobertura Universal do Seguro de Saúde , Humanos , Estudos Longitudinais , Programas Nacionais de Saúde , República da Coreia/epidemiologia
15.
Oncoimmunology ; 10(1): 1904573, 2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33854823

RESUMO

The tumor microenvironment (TME) within mucosal neoplastic tissue in oral cancer (ORCA) is greatly influenced by tumor-infiltrating lymphocytes (TILs). Here, a clustering method was performed using CIBERSORT profiles of ORCA data that were filtered from the publicly accessible data of patients with head and neck cancer in The Cancer Genome Atlas (TCGA) using hierarchical clustering where patients were regrouped into binary risk groups based on the clustering-measuring scores and survival patterns associated with individual groups. Based on this analysis, clinically reasonable differences were identified in 16 out of 22 TIL fractions between groups. A deep neural network classifier was trained using the TIL fraction patterns. This internally validated classifier was used on another individual ORCA dataset from the International Cancer Genome Consortium data portal, and patient survival patterns were precisely predicted. Seven common differentially expressed genes between the two risk groups were obtained. This new approach confirms the importance of TILs in the TME and provides a direction for the use of a novel deep-learning approach for cancer prognosis.


Assuntos
Aprendizado Profundo , Neoplasias Bucais , Humanos , Linfócitos do Interstício Tumoral , Prognóstico , Microambiente Tumoral
16.
Biosci Rep ; 41(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33245093

RESUMO

Abdominal aortic aneurysm (AAA), when ruptured, results in high mortality. The identification of molecular pathways involved in AAA progression is required to improve AAA prognosis. The aim of the present study was to assess the key genes for the progression of AAA and their functional role. Genomic and clinical data of three independent cohorts were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) (GSE57691, GSE7084, and GSE98278). To develop AAA diagnosis and progression-related differentially expressed genes (DEGs), we used a significance analysis of microarray (SAM). Spearman correlation test and gene set analysis were performed to identify potential enriched pathways for DEGs. Only the Frizzled-related protein (FRZB) gene and chromosome 1 open reading frame 24 (C1orf24) exhibited significant down-regulation in all analyses. With FRZB, the pathways were associated with RHO GTPase and elastin fiber formation. With C1orf24, the pathways were elastic fiber formation, extracellular matrix organization, and cell-cell communication. Since only FRZB was evolutionally conserved in the vertebrates, function of FRZB was validated using zebrafish embryos. Knockdown of frzb remarkably reduced vascular integrity in zebrafish embryos. We believe that FRZB is a key gene involved in AAA initiation and progression affecting vascular integrity.


Assuntos
Aneurisma da Aorta Abdominal/genética , Vasos Sanguíneos/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Idoso , Animais , Aneurisma da Aorta Abdominal/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Fases de Leitura Aberta , Peixe-Zebra/embriologia
17.
Front Endocrinol (Lausanne) ; 12: 724278, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35145474

RESUMO

Introduction: It is well known that the presence of diabetes significantly affects the progression of periodontitis and that periodontitis has negative effects on diabetes and diabetes-related complications. Although this two-way relationship between type 2 diabetes and periodontitis could be understood through experimental and clinical studies, information on common genetic factors would be more useful for the understanding of both diseases and the development of treatment strategies. Materials and Methods: Gene expression data for periodontitis and type 2 diabetes were obtained from the Gene Expression Omnibus database. After preprocessing of data to reduce heterogeneity, differentially expressed genes (DEGs) between disease and normal tissue were identified using a linear regression model package. Gene ontology and Kyoto encyclopedia of genes and genome pathway enrichment analyses were conducted using R package 'vsn'. A protein-protein interaction network was constructed using the search tool for the retrieval of the interacting genes database. We used molecular complex detection for optimal module selection. CytoHubba was used to identify the highest linkage hub gene in the network. Results: We identified 152 commonly DEGs, including 125 upregulated and 27 downregulated genes. Through common DEGs, we constructed a protein-protein interaction and identified highly connected hub genes. The hub genes were up-regulated in both diseases and were most significantly enriched in the Fc gamma R-mediated phagocytosis pathway. Discussion: We have identified three up-regulated genes involved in Fc gamma receptor-mediated phagocytosis, and these genes could be potential therapeutic targets in patients with periodontitis and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/genética , Periodontite/genética , Adulto , Idoso , Biologia Computacional , Bases de Dados Genéticas , Regulação para Baixo , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fagocitose/genética , Mapas de Interação de Proteínas , Receptores de IgG , Transcriptoma , Regulação para Cima
18.
Front Genet ; 12: 743786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646310

RESUMO

Glioma is the most common primary malignant tumor that occurs in the central nervous system. Gliomas are subdivided according to a combination of microscopic morphological, molecular, and genetic factors. Glioblastoma (GBM) is the most aggressive malignant tumor; however, efficient therapies or specific target molecules for GBM have not been developed. We accessed RNA-seq and clinical data from The Cancer Genome Atlas, the Chinese Glioma Genome Atlas, and the GSE16011 dataset, and identified differentially expressed genes (DEGs) that were common to both GBM and lower-grade glioma (LGG) in three independent cohorts. The biological functions of common DEGs were examined using NetworkAnalyst. To evaluate the prognostic performance of common DEGs, we performed Kaplan-Meier and Cox regression analyses. We investigated the function of SOCS3 in the central nervous system using three GBM cell lines as well as zebrafish embryos. There were 168 upregulated genes and 50 downregulated genes that were commom to both GBM and LGG. Through survival analyses, we found that SOCS3 was the only prognostic gene in all cohorts. Inhibition of SOCS3 using siRNA decreased the proliferation of GBM cell lines. We also found that the zebrafish ortholog, socs3b, was associated with brain development through the regulation of cell proliferation in neuronal tissue. While additional mechanistic studies are necessary, our results suggest that SOCS3 is an important biomarker for glioma and that SOCS3 is related to the proliferation of neuronal tissue.

19.
Melanoma Res ; 30(6): 543-547, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33003118

RESUMO

Cutaneous melanoma is the most common cause of skin cancer-related deaths worldwide. There is an urgent need to identify prognostic biomarkers to facilitate decision-making for treatment of metastatic cutaneous melanoma. Gene expression microarrays and RNA-seq technology have recently improved or changed current prognostic and therapeutic strategies for several cancers. However, according to the current melanoma staging system, prognosis is almost entirely dependent on clinicopathological features. To identify novel prognostic biomarkers, we investigated gene expression and clinical data for patients with cutaneous melanoma from three cohorts of The Cancer Genome Atlas and Gene Expression Omnibus. Kaplan-Meier survival analysis using median values of each gene as cutoff value revealed that nine genes (ABCC3, CAPS2, CCR6, CDCA8, CLU, DPF1, PTK2B, SATB1, and SYNE1) were statistically significant prognostic biomarkers of metastatic cutaneous melanoma in all three independent cohorts. Low expression of two genes (CDCA8 and DPF1) and high expression of seven genes (ABCC3, CAPS2, CCR6, CLU, PTK2B, SATB1, and SYNE) were significantly associated with positive metastatic cutaneous melanoma prognoses. In conclusion, we suggest nine novel prognostic biomarkers for cutaneous metastatic melanoma.


Assuntos
Melanoma/genética , RNA Mensageiro/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Melanoma Maligno Cutâneo
20.
Anticancer Res ; 40(10): 5601-5609, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988884

RESUMO

BACKGROUND/AIM: Since pathways involving LRRC17 are related to the survival of patients with various cancers, we analyzed LRRC17 as a prognostic gene in serous ovarian cancer. MATERIALS AND METHODS: Data were collected from Gene Expression Omnibus (GSE9891, GSE13876, and GSE26712) and The Cancer Genome Atlas (TCGA). We performed survival analyses using C statistics, area under the curve, survival plot with optimal cutoff level, and cox proportional regression. Zebrafish embryos were used as an in vivo model. RESULTS: The prognosis of patients with high LRRC17 expression was poorer than that of patients with low LRRC17 expression. Multivariate regression analysis showed that LRRC17 expression, age, and stage were independently related with survival. Knockdown of lrrc17 reduced survival rate and delayed development in zebrafish embryos. We also found that lrrc17 is important for cell viability by protecting from p53-dependent apoptosis. CONCLUSION: LRRC17 could be a prognostic gene in ovarian cancer as it regulates cancer cell viability through the p53 pathway.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ovarianas/genética , Proteínas/genética , Proteína Supressora de Tumor p53/genética , Idoso , Apoptose/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico
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