Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA294509 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2229270_1.fastq.gz | Fastqsanger.gz | |||
| SRR2229270_2.fastq.gz | Fastqsanger.gz | |||
| SRR2229271_1.fastq.gz | Fastqsanger.gz | |||
| SRR2229271_2.fastq.gz | Fastqsanger.gz | |||
| SRR2229272_1.fastq.gz | Fastqsanger.gz |
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Project description:Oral malignancies are among the top most deadly cancers in the world. Early diagnosis of oral premalignant and malignant lesions is essential for treatment decision-making and prognosis improvement. In this study, we systematically evaluated the gene expression patterns during the pathogenesis of oral moderate dysplasia. RNA sequencing detected 21556 genes in moderate dysplasia and paired normal tissues from three patients. Hierarchical clustering analysis revealed distinct gene expression patterns between the moderate dysplasia samples. 346 differentially expressed genes that may contribute to the pathogenesis of moderate dysplasia were identified. Among these genes, ISG15 and MAGEA family showed different transcription profiles that close related with the alterations of gene expression patterns in moderate dysplasia samples and paired normal tissues. We speculated that, as the potential marker to signal the risk of malignant transformation, ISG15 and MAGEA together with their close related misexpressed genes may involve in two different pathways during the malignant conversion from oral dysplasia to oral squamous cell carcinoma.
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Project description:Understanding the dynamics of the immune microenvironment is critical to the development of immuno-prevention strategies for the prevention of oral potentially malignant disorders transformation to oral squamous cell carcinoma (OSCC). We generated gene expression profiles of the microdissected epithelial and stromal compartments normal mucosa, hyperplasia, dysplasia and invasive tumors in the 4-nitroquinolein (4-NQO) murine model of oral carcinogenesis. Most gene expression changes were observed in the stromal compartment and related to immune biological processes. Immune cell deconvolution identified infiltration by the macrophage population as the most important quantitatively especially at the stage of dysplasia. In 86 patients with oral leukoplakia, three M2 macrophages signatures were independently associated and highly predictive of improved oral cancer-free survival.
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Project description:micro-RNA in cancer-associated fibroblasts in oral squamous cell carcinoma vs. dysplasia-associated fibroblasts from dysplastic oral lesions vs. normal fibroblasts from normal oral mucosa from healthy individual.
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Project description:The aim of the study was to address the concept of field cancerization in oral cancer. The presence of genomic aberrations, indicative of chromosomal instability (CIN), in oral distant fields (ODFs) of visually normal and non-dysplastic mucosa at the mirror image from concomitant oral potentially malignant lesions (OPMLs) was investigated. This pilot study comprised 16 OPMLs (8 without dysplasia, nd-OPMLs; 8 with dysplasia, d-OPMLs) and 16 ODFs. DNA diploid (DNA Index, DI=1) and aneuploid (DIM-bM-^IM- 1) sublines were detected by high resolution DNA-flow cytometry (FCM) at (hr DNA-FCM) using DAPI stained nuclei suspensions. Nuclei with different DIs were FCM-sorted in order to enrich the epithelial component and to obtain genomic DNA for high resolution oligonucleotide array-Comparative Genomic Hybridization (a-CGH) analysis to provide a genome-wide measurement of DNA copy number aberrations (CNAs). The frequencies of DNA aneuploidy in ODFs and OPMLs were 6.2% and 43.8%, respectively (p=0.037). ODFs and nd-OPMLs were all near-diploid (DIM-bM-^IM- 1 and DIM-bM-^IM-$1.4), while d-OPMLs were also high-aneuploid (DI>1.4). CNA averages were 2.3 in ODFs (1.5 for nd-OPMLs and 3.1 for d-OPMLs), and 7.325 in OPMLs (3.0 in nd-OPMLs; 11.6 in d-OPMLs). CNAs were present in the DNA diploid sublines and often the same CNAs were observed in both ODFs and corresponding OPMLs DNA aneuploid sublines and CNAs in the present series of 16 ODFs are likely to represent early events of the natural history of oral carcinogenesis and to indicate an early onset of the field effect cancerization. Moreover, gains within 20q13.33-qter, 7p22.2-pter and 16p13.3-pter chromosomal regions in ODFs and in the relative OPMLs suggest that specific genes localized in these regions (RTEL1, MAD1L1 and TEL2) might contribute to the ODF/d-OPML transition. We analyzed: 8 samples of oral potentially malignant lesions with dysplasia, 8 samples of oral potentially malignant lesions without dysplasia and for each patient a corresponding oral distant field of visually normal mucosa.
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Project description:A better understanding of molecular changes during oral tumorigenesis may help defining new personalized prevention strategies. In order to test this hypothesis, we analyzed whole-genome expression changes in a murine model of oral carcinogenesis, induced by an oral carcinogen (4-NQO) We generated genome-wide expression profiles of microdissected cells from murine tongue at each step of oral tumorigenesis: normal mucosa, hyperplasia, dysplasia and tumor.
2016-12-06 | GSE75421 | GEO
Project description:Analysis of various of up-regulated and down-regulated genes in normal oral mucosa and different stages of OSF. The report provides a data analysis methodology for identification of co-expressed gene patterns, as emerging clusters, in global transcriptome of oral mucosal pre-malignant and malignant conditions in comparison to their normal counterparts. Microarray based study of global gene expression is often used to extract molecular signatures underlying cancer progression. Such endeavors endorse self organizing map, a type of artificial neural network to analyze high dimensional pre-processed transcriptome data to segregate hotspot genes in component plane for disease subtypes. This report provides a data analysis methodology for identification of co-expressed gene patterns, as emerging clusters, in global transcriptome of oral mucosal pre-malignant and malignant conditions in comparison to their normal counterparts. Four exclusive cluster patterns, each involving 100 − 300 genes, were identified from component planes for oral study groups. Gene expression associated with each pattern belonged to 32 biological processes. The transcription and RNA processing, and angiogenesis were dominant in normal oral condition, while immunity, cellular differentiation and migration, neuron signalling, connective tissue organization, tumor suppression, and enzyme regulation showed predominance in oral squamous cell carcinoma. In dysplasia skeletal and ligament development processes were dominant while in non-dysplastic sub-mucous fibrosis cytoskeleton reorganization and neuron signalling were pre-dominant. In dysplasia an intermediate pattern with nine different dominant functional processes was identified. This analysis demonstrated utility of self organizing map to capture dominant enriched patterns as visual plots and revealed six common biological processes like transcription and RNA processing, cytoskeleton reorganization, angiogenesis, immunity, neuron signalling, and connective tissue remodeling in the pathogenesis of oral cancer. In fact it could provide an intuitive understanding of molecular course in carcinogenesis and may contribute for combinatorial biomarker discovery.
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Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
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