RESUMO
Deep understanding of the genomic and immunological differences between Chinese and Western lung cancer patients is of great importance for target therapy selection and development for Chinese patients. Here we report an extensive molecular and immune profiling study of 245 Chinese patients with non-small cell lung cancer. Tumor-infiltrating lymphocyte estimated using immune cell signatures is found to be significantly higher in adenocarcinoma (ADC, 72.5%) compared with squamous cell carcinoma (SQCC, 54.4%). The correlation of genomic alterations with immune signatures reveals that low immune infiltration was associated with EGFR mutations in ADC samples, PI3K and/or WNT pathway activation in SQCC. While KRAS mutations are found to be significantly associated with T cell infiltration in ADC samples. The SQCC patients with high antigen presentation machinery and cytotoxic T cell signature scores are found to have a prolonged overall survival time.
Assuntos
Adenocarcinoma de Pulmão/genética , Povo Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/mortalidade , Idoso , Apresentação de Antígeno/genética , Apresentação de Antígeno/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Conjuntos de Dados como Assunto , Receptores ErbB/genética , Feminino , Genômica , Humanos , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Linfócitos T Citotóxicos/imunologia , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/imunologiaAssuntos
Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Imidazolinas/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Humanos , Imidazolinas/efeitos adversos , Leucemia Mieloide Aguda/enzimologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-mdm2/metabolismoRESUMO
Intraspecific hybrids between the Arabidopsis thaliana accessions C24 and Landsberg erecta have strong heterosis. The reciprocal hybrids show a decreased level of 24-nt small RNA (sRNA) relative to the parents with the decrease greatest for those loci where the parents had markedly different 24-nt sRNA levels. The genomic regions with reduced 24-nt sRNA levels were largely associated with genes and their flanking regions indicating a potential effect on gene expression. We identified several examples of genes with altered 24-nt sRNA levels that showed correlated changes in DNA methylation and expression levels. We suggest that such epigenetically generated differences in gene activity may contribute to hybrid vigor and that the epigenetic diversity between ecotypes provides increased allelic (epi-allelic) variability that could contribute to heterosis.
Assuntos
Arabidopsis/metabolismo , Quimera/metabolismo , Epigênese Genética/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , RNA de Plantas/metabolismo , RNA Interferente Pequeno/metabolismo , Arabidopsis/genética , Quimera/genética , Metilação de DNA/fisiologia , Loci Gênicos/fisiologia , RNA de Plantas/genética , RNA Interferente Pequeno/genéticaRESUMO
We established a protocol of the SuperSAGE technology combined with next-generation sequencing, coined "High-Throughput (HT-) SuperSAGE". SuperSAGE is a method of digital gene expression profiling that allows isolation of 26-bp tag fragments from expressed transcripts. In the present protocol, index (barcode) sequences are employed to discriminate tags from different samples. Such barcodes allow researchers to analyze digital tags from transcriptomes of many samples in a single sequencing run by simply pooling the libraries. Here, we demonstrated that HT-SuperSAGE provided highly sensitive, reproducible and accurate digital gene expression data. By increasing throughput for analysis in HT-SuperSAGE, various applications are foreseen and several examples are provided in the present study, including analyses of laser-microdissected cells, biological replicates and tag extraction using different anchoring enzymes.
Assuntos
Perfilação da Expressão Gênica/métodos , Análise de Sequência de DNA/métodos , Animais , Sequência de Bases , Enzimas de Restrição do DNA/metabolismo , Biblioteca Gênica , Reação em Cadeia da Polimerase , Reprodutibilidade dos TestesRESUMO
Brachyspira hyodysenteriae is an anaerobic intestinal spirochete that colonizes the large intestine of pigs and causes swine dysentery, a disease of significant economic importance. The genome sequence of B. hyodysenteriae strain WA1 was determined, making it the first representative of the genus Brachyspira to be sequenced, and the seventeenth spirochete genome to be reported. The genome consisted of a circular 3,000,694 base pair (bp) chromosome, and a 35,940 bp circular plasmid that has not previously been described. The spirochete had 2,122 protein-coding sequences. Of the predicted proteins, more had similarities to proteins of the enteric Escherichia coli and Clostridium species than they did to proteins of other spirochetes. Many of these genes were associated with transport and metabolism, and they may have been gradually acquired through horizontal gene transfer in the environment of the large intestine. A reconstruction of central metabolic pathways identified a complete set of coding sequences for glycolysis, gluconeogenesis, a non-oxidative pentose phosphate pathway, nucleotide metabolism, lipooligosaccharide biosynthesis, and a respiratory electron transport chain. A notable finding was the presence on the plasmid of the genes involved in rhamnose biosynthesis. Potential virulence genes included those for 15 proteases and six hemolysins. Other adaptations to an enteric lifestyle included the presence of large numbers of genes associated with chemotaxis and motility. B. hyodysenteriae has diverged from other spirochetes in the process of accommodating to its habitat in the porcine large intestine.
