RESUMO
Clinically relevant biomarkers are useful to determine cancer patients' prognosis and treatments. To discover new putative biomarkers, we performed in silico analysis of a 325-gene panel previously associated with breast epithelial cell biology and clinical outcomes. Sixteen public datasets of microarray samples representing 8 cancer types and a total of 3,663 patients' samples were used for the analyses. Feature selection was used to identify the best subsets of the 325 genes for each classification, and linear discriminant analysis was used to quantify the accuracy of the classifications. A subset of 102 of the 325 genes were found to be housekeeping (HK) genes, and the classifications were repeated using only the 102 HK subset. The 325-gene panel and 102 HK subset were able to distinguish colon, gastric, lung, ovarian, pancreatic, and prostate tumors and leukemia from normal adjacent tissue, and classify disease subtypes of breast and lung cancers and leukemia with 70% or higher accuracy. HK genes have been overlooked as potential biomarkers due to their relative stability. This study describes a set of HK genes as putative biomarkers applicable to multiple cancer types worth following in subsequent validation studies.
Assuntos
Humanos , Masculino , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Fenótipo , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Genes EssenciaisRESUMO
The aim of this study was to identify genes with higher expression in solid tumor cells by comparing human tumor biopsies with healthy blood samples using both in silico statistical analysis and experimental validations. This approach resulted in a novel panel of 80 RNA biomarkers with high discrimination power to detect circulating tumor cells in blood samples. To identify the 80 RNA biomarkers, Affymetrix HG-U133 plus 2.0 microarrays datasets were used to compare breast tumor tissue biopsies and breast cancer cell lines with blood samples from patients with conditions other than cancer. A total of 859 samples were analyzed at the discovery stage, consisting of 417 mammary tumors, 41 breast lines, and 401 control samples. To confirm this discovery, external datasets of eight types of tumors were used, and experimental validation studies (NanoString n-counter gene expression assay) were performed, totaling 5028 samples analyzed. In these analyses, the 80 biomarkers showed higher expression in all solid tumors analyzed relative to healthy blood samples. Experimental validation studies using NanoString assay confirmed the results were not dependent of the gene expression platform. A panel of 80 RNA biomarkers was described here, with the potential to detect solid tumor cells present in the blood of multiple tumor types.
Assuntos
Biomarcadores Tumorais , Neoplasias/genética , Transcriptoma , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Células Neoplásicas Circulantes/metabolismo , Reprodutibilidade dos TestesRESUMO
Mareks disease (MD), a lymphoproliferative disorder of chickens caused by the MD virus (MDV), is economically significant. The resistance/susceptibility to MD is controlled by host genetics. The host response to different virus strains varies. The pathogenicity of REV-LTR deleted GX0101LTR MDV has been previously reported. However, the precise molecular mechanism of the response of chickens to GX0101LTR remains unclear. The current study aimed at identifying the genes and pathways involved in the response to GX0101LTR virus infection in specific pathogen-free chicken embryo fibroblast cells using global transcriptome analysis. A total of 1,633 genes associated with GX0101LTR infection were identified. Functional analysis showed that the cytokine-cytokine receptor interaction plays an important role in the response to GX0101LTR infection.
Assuntos
Animais , Embrião de Galinha , Doença de Marek/diagnóstico , Doença de Marek/embriologia , Transcriptoma/fisiologiaRESUMO
Mareks disease (MD), a lymphoproliferative disorder of chickens caused by the MD virus (MDV), is economically significant. The resistance/susceptibility to MD is controlled by host genetics. The host response to different virus strains varies. The pathogenicity of REV-LTR deleted GX0101LTR MDV has been previously reported. However, the precise molecular mechanism of the response of chickens to GX0101LTR remains unclear. The current study aimed at identifying the genes and pathways involved in the response to GX0101LTR virus infection in specific pathogen-free chicken embryo fibroblast cells using global transcriptome analysis. A total of 1,633 genes associated with GX0101LTR infection were identified. Functional analysis showed that the cytokine-cytokine receptor interaction plays an important role in the response to GX0101LTR infection.(AU)
Assuntos
Animais , Embrião de Galinha , Doença de Marek/diagnóstico , Doença de Marek/embriologia , Transcriptoma/fisiologiaRESUMO
Toxigenic strains of Clostridium difficile may be disseminating. Here we prospectively screened patients with nosocomial diarrhoea in two hospitals in Brazil. To identify C. difficile polymerase chain reaction ribotypes 027/078 strains, we used high resolution melting and multiplex polymerase chain reaction. Among 116 screened patients, 11 were positive for C. difficile. The polymerase chain reaction ribotypes 027/078 strains were not identified in this study.
Assuntos
Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Infecção Hospitalar/microbiologia , Diarreia/microbiologia , Ribotipagem , Brasil , Fezes/microbiologia , Humanos , Reação em Cadeia da Polimerase , Estudos ProspectivosRESUMO
Human bone marrow-derived mesenchymal stem cells (hMSCs) have the capacity to differentiate into osteoblasts during osteogenesis. Several studies attempted to identify osteogenesis-related genes in hMSCs. Although HOX genes are known to play a pivotal role in skeletogenesis, their function in the osteogenesis of hMSCs has not yet been investigated in detail. Our aim was to characterize the expression of 37 HOX genes by multiplex RT-PCR to identify the ones most probably involved in osteogenic differentiation. The results showed that the expression patterns of four HOX genes were altered during this process. In particular, the expression levels of HOXC13 and HOXD13 were dramatically changed. Real-time PCR and Western blot analysis were performed in order to further analyze the expression of HOXC13 and HOXD13. The qRT-PCR results showed that transcription of HOXC13 was up-regulated by up to forty times, whereas that of HOXD13 was down-regulated by approximately five times after osteogenic differentiation. The Western blot results for the HOXC13 and HOXD13 proteins also corresponded well with the real-time PCR result. These findings suggest that HOXC13 and HOXD13 might be involved in the osteogenic differentiation of hMSCs.