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Multi-omics screening of differentially expressed genes and related mechanisms of gastric neuroendocrine tumors

ABSTRACT: This project uses transcriptome sequencing combined with proteomic analysis technology to find the mRNA and proteins differentially expressed between G-NENs and normal gastric mucosal tissues. Through bioinformatic analysis, potentially meaningful functional genes and their signaling pathways are screened, and the protein interaction network (PPI) of differentially expressed genes is constructed. Cytologically verified the function of the target genes and their regulatory pathways. By detecting the expression level of the target protein in clinical samples, the clinical application value of the target gene in G-NENs was clarified, and the possibility of serving as a molecular marker of G-NENs to judge the disease progression, treatment and prognosis was comprehensively evaluated. The ultimate goal is to discover the ultimate goal of target genes affecting the occurrence, development and prognosis of G-NENs.

ORGANISM(S): Homo Sapiens

SUBMITTER: Shengmian Li

PROVIDER: PXD052328 | iProX | Fri May 17 00:00:00 BST 2024

REPOSITORIES: iProX

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Project description:Background: This study aimed to screen the signaling axis of epigenetic modification in serum exosomes of ovarian cancer patients based on sequencing technology and raw signal analysis, perform an in-depth study of the potential mechanism of action of ovarian cancer, predict potential therapeutic targets and perform a survival prognosis analysis of potential targets Methods: Serum exosomes from three ovarian cancer patients were selected as the experimental group, and serum exosomes from three uterine fibroid patients were selected as the control group. The whole transcriptomes of serum exosomes were used to obtain differentially expressed lncRNAs and mRNAs in ovarian cancer. The miRcode database and miRNA target gene prediction website were used to predict the target genes. Cytoscape software was used to draw a ceRNA network model of epigenetic modification of ovarian cancer serum exosomes, and R language was used for GO and KEGG enrichment analyses of the target genes. Finally, the TCGA website was used to download clinical and expression data related to ovarian cancer, and the common potential target genes obtained in the previous period were analyzed for survival. Results: A total of 117 differentially expressed lncRNAs and 513 differentially expressed mRNAs (P < 0.05, |log2 FC|≥ 1.0) were obtained by combining sequencing data and raw signal analysis, and 841 predicted target genes were reciprocally mapped by combining the miRcode database and the miRNA target gene prediction website, resulting in 11 potential target genes related to ovarian cancer (FGFR3, BMPR1B, TRIM29, FBN2, PAPPA, CCDC58, IGSF3, FBXO10, GPAM, HOXA10, LHFPL4). Survival prognosis analysis of the above 11 target genes revealed that the survival curve was statistically significant (P < 0.05) for HOXA10-only genes but not for the other genes. Through enrichment analysis, we found that the above target genes were mainly involved in biological processes such as regulation of transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor-activated receptor activity, and GABA receptor binding, and were mainly enriched in metabolism pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, central carbon metabolism of cancer, and resistance to EGFR tyrosine kinase inhibitors. Conclusions: The serum exosomal DIO3OS-hsa-miR-27a-3p-HOXA10 epigenetic modification signaling axis affects ovarian cancer development and disease survival prognosis by targeting transcriptional dysregulation pathways in cancer.

Project description:Periodontal regeneration study. Periodontitis is a common chronic inflammatory disease which may lead to tooth loss. The ultimate goal of periodontal therapy is complete regeneration of the tissues lost as a result of periodontitis. However, most regenerative clinical procedures are unpredictable, largely because there is a lack of understanding of how the various tissues comprising the periodontium (gingival epithelium, gingival connective tissue, periodontal ligament, aveolar bone and cementum) interact during the regenerative process. The aim of this study was to investigate the molecular mechanisms that are involved in periodontal regeneration. For this purpose, paired sets of gingival, ligament and regenerating cells were isolated from patients that have been treated for periodontitis via a regenerative surgical procedure. A microarray analysis using the Hu133A Affymetrix arrays was used to identify the genes and pathways that were characteristic of the three different tissues. We have identified over 500 transcripts in global comparison and intrapatient comparisons that were differentially expressed between ligament and gingival samples, and approximately 30 transcripts that characterized the regenerating cell population. By using a functional classification based on Gene Ontology we were able to group the transcripts into 12 groups. Proteases/Protease inhibitors were differentially expressed between the ligament and gingiva highlighting high ECM remodelling activity by gingival cells. On the other hand, ligament cells were shown to have increased protein synthesis by increasing their nucleolar and ribosomal gene complement. We were able to identify 57 various DNA binding proteins, among them were some well characterised transcription factors, transcriptional regulators, including DNA polymerases and transcriptional co-activators. Furthermore, we have also identified changes in expression of their targets in the two tissues. This is the first study to characterise the gene expression profile of periodontal regenerating cells and allowed us to gain valuable insights into the cellular and molecular mechanisms that occur during the regenerative process. We have identified signalling pathways which are consistent with clinical observations of the regenerative properties of gingival and periodontal ligament cells. These pathways provide candidate targets that can be manipulated in order to achieve a superior regenerative clinical outcome.

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Multi-omics screening of differentially expressed genes and related mechanisms of gastric neuroendocrine tumors

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