Preliminary screening of gastric cancer related transcripts based on nanometric magnetic beads

2020 ◽  
Vol 10 (9) ◽  
pp. 1490-1497
Author(s):  
Diqun Liu ◽  
Wenbo Cao ◽  
Guangsheng Hu ◽  
Nannan Wang ◽  
Weiwei Zhou
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Magnetic Beads ◽  
Expression Profiles ◽  
Gastrointestinal Surgery ◽  
Gene Expression Profiles ◽  
Magnetic Bead ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Low Levels

The aim of this study was to use current genomics methodologies to screen for gastric cancer (GC)-related gene expression and to compare expression levels associated with GC and paracancerous tissues. These findings will be considered together with patient clinicopathological data with the goal of identifying new tumor markers and novel directions for diagnosis and treatment. GC-associated gene expression profiles were identified in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases; these resources facilitated identification of genes that were differentially expressed in GC and adjacent normal tissues. Genomics screening identified ∼49 genes that were expressed at comparatively high levels and 65 genes that were expressed at comparatively low levels in association with GC. Moreover, specimens from fifty-six patients diagnosed with GC who underwent gastrointestinal surgery between March 2017 to September 2018 were used to generate RNA that was evaluated by real-time fluorescence quantitative PCR in order to confirm differential expression of genes encoding orosomucoid 1 (ORM1), hepsin (HPN), uridine phosphorylase 1 (UPP1), and glycoprotein nonmetastatic melanoma protein B (GPNMB). The nucleic acid of these samples was extracted by nanometric magnetic bead method. Among our findings, GPNMB was expressed at relatively high levels in association GC, while both ORM1 and HPN are expressed at relatively low levels in these tissues and expression of UPP1 remained unchanged. Taken together, our findings suggest that genomics methodologies can be used to identify differentially expressed genes in a comparison of GC to adjacent paracancerous tissue. Our findings also suggest that the transmembrane glycoprotein GPNMB may play a role in promoting the incidence and development of GC.

scholarly journals Tumor microenvironment characterization in stage IV gastric cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Xianxue Zhang ◽  
Feng Yang ◽  
Zhenbao Wang
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Stage Iv ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Stage Iv Gastric Cancer ◽  
Th 17 ◽  
Cancer Genome Atlas

Abstract Immunotherapy is remarkably affected by the immune environment of the principal tumor. Nonetheless, the immune environment’s clinical relevance in stage IV gastric cancer (GC) is largely unknown. The gene expression profiles of 403 stage IV GC patients in the three cohorts: GEO (Gene Expression Omnibus, GSE84437 (n=292) and GSE62254 (n=77), and TCGA (The Cancer Genome Atlas, n=34) were used in the present study. Using four publicly available stage IV GC expression datasets, 29 immune signatures were expression profiled, and on this basis, we classified stage IV GC. The classification was conducted using the hierarchical clustering method. Three stage IV GC subtypes L, M, and H were identified representing low, medium, and high immunity, respectively. Immune correlation analysis of these three types revealed that Immune H exhibited a better prognostic outcome as well as a higher immune score compared with other subtypes. There was a noticeable difference in the three subgroups of HLA genes. Further, on comparing with other subtypes, CD86, CD80, CD274, CTLA4, PDCD1, and PDCD1LG2 had higher expression in the Immunity H subtype. In stage IV GC, potentially positive associations between immune and pathway activities were displayed, due to the enrichment of pathways including TNF signaling, Th-17 cell differentiation, and JAK-STAT signaling pathways in Immunity H vs Immunity L subtypes. External cohorts from TCGA cohort ratified these results. The identification of stage IV GC subtypes has potential clinical implications in stage IV GC treatment.

Effect of Imids on Gene Expression Profiles of Fresh Human Myeloma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5013-5013
Author(s):  
Ines Tagoug ◽  
Adriana Plesa ◽  
Julie Vendrell ◽  
Charles Dumontet
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Family Member ◽  
Magnetic Beads ◽  
Expression Profiles ◽  
Calf Serum ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Myeloma Cells ◽  
Human Myeloma Cells

Abstract Abstract 5013 Immunomodulatory drugs represent a major therapeutic advance in the treatment of patients with multiple myeloma. While these agents appear to exert various effects on the microenvironment, including effect on immune cells and angiogenesis, a direct effect on the tumor cells themselves is also likely. To describe and compare the effect of the three clinically available agents (thalidomide, lenalidomide, pomalidomide) we analyzed the gene expression profiles of fresh human myeloma cells exposed to thalidomide, lenalidomide or pomalidomide, using high density DNA arrays. Fresh human myeloma samples were obtained from bone marrow aspirates of patients with myeloma, and myeloma cells were immunopurified using anti CD138 magnetic beads. Purified myeloma cells (1.106 cells/ml) were incubated for 24 hours in RPMI 1640 medium supplemented with 10% fetal calf serum under each of the four following conditions: 1) DMSO; 2) thalidomide 40 microM; 3) lenalidomide 1 microM; 4) pomalidomide 100 nM. These levels are achievable in the plasma of MM pts. Pangenomic array experiments were performed usingWhole Human Genome 4 × 44K Agilent one-color microarrays. Data were normalized using the quantile normalization method. Samples were analysed for differentially expressed genes, taking into account both the level of significance and the fold-change. Ten evaluable samples were processed. Exposure to thalidomide, lenalidomide and pomalidomide induced differential expression of 36, 50 and 75 genes, respectively, in comparison to DMSO-exposed controls, the total list including 101 genes. Twelve of these were found to be differentially expressed after exposure to all of the three agents, including trophoblast glycoprotein, WAS protein family member 1, dickkopf homolog 1, pentraxin-related gene, CD28, interleukin 12B, tissue factor pathway inhibitor 2, phospholipase A2, dehydrogenase/reductase (SDR family) member 9, hypothetical LOC145788 and betacellulin. These commonly altered genes could be mechanistically involved in themultiple activities of these agents in multiple myeloma or may represent epiphenoma mechanistically unrelated to drug-induced cell death. Genes differentially expressed between the treatment with each of these agents could be indicative of the different and non-overlapping actions these agents have in multiple myeloma. An example of this is the recent demonstration that pomalidomide is clinically active in lenalidomide refractory patients. These results suggest that exposure to IMIDs induce various intracellular signalization pathways in myeloma cells which might be involved in the cytotoxic activity of these compounds. Disclosures: Dumontet: Celgene: Research Funding.

scholarly journals Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
H. Sallinen ◽  
S. Janhonen ◽  
P. Pölönen ◽  
H. Niskanen ◽  
O. H. Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Carcinoma ◽  
Differentially Expressed Genes ◽  
Cellular Proliferation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Differentially Expressed

Abstract Background High grade serous ovarian carcinoma (HGSOC) is the most common subtype of epithelial ovarian cancers (EOC) with poor prognosis. In most cases EOC is widely disseminated at the time of diagnosis. Despite the optimal cytoreductive surgery and chemotherapy most patients develop chemoresistance, and the 5-year overall survival being only 25–35%. Methods Here we analyzed the gene expression profiles of 10 primary HGSOC tumors and 10 related omental metastases using RNA sequencing and identified 100 differentially expressed genes. Results The differentially expressed genes were associated with decreased embryogenesis and vasculogenesis and increased cellular proliferation and organismal death. Top upstream regulators responsible for this gene signature were NR5A1, GATA4, FOXL2, TP53 and BMP7. A subset of these genes were highly expressed in the ovarian cancer among the cancer transcriptomes of The Cancer Genome Atlas. Importantly, the metastatic gene signature was suggestive of poor survival in TCGA data based on gene enrichment analysis. Conclusion By comparing the gene expression profiles of primary HGSOC tumors and their matched metastasis, we provide evidence that a signature of 100 genes is able to separate these two sample types and potentially predict patient survival. Our study identifies functional categories of genes and transcription factors that could play important roles in promoting metastases and serve as markers for cancer prognosis.

4 Molecularly guided multiplexed digital spatial analysis reveals differential gene expression profiles in the WNT-β-catenin pathway between melanoma and prostate tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A4-A4
Author(s):  
Anushka Dikshit ◽  
Dan Zollinger ◽  
Karen Nguyen ◽  
Jill McKay-Fleisch ◽  
Kit Fuhrman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Single Molecule ◽  
Spatial Information ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Fluorescence Assay ◽  
Differentially Expressed ◽  
Tumor Type ◽  
Prostate Tumors

BackgroundThe canonical WNT-β-catenin signaling pathway is vital for development and tissue homeostasis but becomes strongly tumorigenic when dysregulated. and alter the transcriptional signature of a cell to promote malignant transformation. However, thorough characterization of these transcriptomic signatures has been challenging because traditional methods lack either spatial information, multiplexing, or sensitivity/specificity. To overcome these challenges, we developed a novel workflow combining the single molecule and single cell visualization capabilities of the RNAscope in situ hybridization (ISH) assay with the highly multiplexed spatial profiling capabilities of the GeoMx™ Digital Spatial Profiler (DSP) RNA assays. Using these methods, we sought to spatially profile and compare gene expression signatures of tumor niches with high and low CTNNB1 expression.MethodsAfter screening 120 tumor cores from multiple tumors for CTNNB1 expression by the RNAscope assay, we identified melanoma as the tumor type with the highest CTNNB1 expression while prostate tumors had the lowest expression. Using the RNAscope Multiplex Fluorescence assay we selected regions of high CTNNB1 expression within 3 melanoma tumors as well as regions with low CTNNB1 expression within 3 prostate tumors. These selected regions of interest (ROIs) were then transcriptionally profiled using the GeoMx DSP RNA assay for a set of 78 genes relevant in immuno-oncology. Target genes that were differentially expressed were further visualized and spatially assessed using the RNAscope Multiplex Fluorescence assay to confirm GeoMx DSP data with single cell resolution.ResultsThe GeoMx DSP analysis comparing the melanoma and prostate tumors revealed that they had significantly different gene expression profiles and many of these genes showed concordance with CTNNB1 expression. Furthermore, immunoregulatory targets such as ICOSLG, CTLA4, PDCD1 and ARG1, also demonstrated significant correlation with CTNNB1 expression. On validating selected targets using the RNAscope assay, we could distinctly visualize that they were not only highly expressed in melanoma compared to the prostate tumor, but their expression levels changed proportionally to that of CTNNB1 within the same tumors suggesting that these differentially expressed genes may be regulated by the WNT-β-catenin pathway.ConclusionsIn summary, by combining the RNAscope ISH assay and the GeoMx DSP RNA assay into one joint workflow we transcriptionally profiled regions of high and low CTNNB1 expression within melanoma and prostate tumors and identified genes potentially regulated by the WNT- β-catenin pathway. This novel workflow can be fully automated and is well suited for interrogating the tumor and stroma and their interactions.GeoMx Assays are for RESEARCH ONLY, not for diagnostics.

scholarly journals Comprehensive analysis of the gene expression profiles in human gastric cancer cell lines

Oncogene ◽  
2002 ◽  
Vol 21 (42) ◽  
pp. 6549-6556 ◽  
Author(s):  
Jiafu Ji ◽  
Xin Chen ◽  
Suet Yi Leung ◽  
Jen-Tsan A Chi ◽  
Kent Man Chu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Comprehensive Analysis ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cell Lines

scholarly journals Integrating Genetic and Transcriptomic Data to Reveal Pathogenesis and Prognostic Markers of Pancreatic Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Kaisong Bai ◽  
Tong Zhao ◽  
Yilong Li ◽  
Xinjian Li ◽  
Zhantian Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Adenocarcinoma ◽  
Somatic Mutation ◽  
Somatic Mutations ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Genomic Variation ◽  
The Cancer Genome Atlas ◽  
Driver Genes

Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies and mortality for PAAD have remained increasing under the conditions of substantial improvements in mortality for other major cancers. Although multiple of studies exists on PAAD, few studies have dissected the oncogenic mechanisms of PAAD based on genomic variation. In this study, we integrated somatic mutation data and gene expression profiles obtained by high-throughput sequencing to characterize the pathogenesis of PAAD. The mutation profile containing 182 samples with 25,470 somatic mutations was obtained from The Cancer Genome Atlas (TCGA). The mutation landscape was generated and somatic mutations in PAAD were found to have preference for mutation location. The combination of mutation matrix and gene expression profiles identified 31 driver genes that were closely associated with tumor cell invasion and apoptosis. Co-expression networks were constructed based on 461 genes significantly associated with driver genes and the hub gene FAM133A in the network was identified to be associated with tumor metastasis. Further, the cascade relationship of somatic mutation-Long non-coding RNA (lncRNA)-microRNA (miRNA) was constructed to reveal a new mechanism for the involvement of mutations in post-transcriptional regulation. We have also identified prognostic markers that are significantly associated with overall survival (OS) of PAAD patients and constructed a risk score model to identify patients’ survival risk. In summary, our study revealed the pathogenic mechanisms and prognostic markers of PAAD providing theoretical support for the development of precision medicine.

scholarly journals Integrative transcriptome data mining for identification of core lncRNAs in breast cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7821 ◽  
Author(s):  
Xiaoming Zhang ◽  
Jing Zhuang ◽  
Lijuan Liu ◽  
Zhengguo He ◽  
Cun Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Prognostic Value ◽  
Early Stage ◽  
Expression Profiles ◽  
Diagnostic Value ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Data Set

Background Cumulative evidence suggests that long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. This study aims to identify lncRNAs that can serve as new biomarkers for breast cancer diagnosis or screening. Methods First, the linear fitting method was used to identify differentially expressed genes from the breast cancer RNA expression profiles in The Cancer Genome Atlas (TCGA). Next, the diagnostic value of all differentially expressed lncRNAs was evaluated using a receiver operating characteristic (ROC) curve. Then, the top ten lncRNAs with the highest diagnostic value were selected as core genes for clinical characteristics and prognosis analysis. Furthermore, core lncRNA-mRNA co-expression networks based on weighted gene co-expression network analysis (WGCNA) were constructed, and functional enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The differential expression level and diagnostic value of core lncRNAs were further evaluated by using independent data set from Gene Expression Omnibus (GEO). Finally, the expression status and prognostic value of core lncRNAs in various tumors were analyzed based on Gene Expression Profiling Interactive Analysis (GEPIA). Results Seven core lncRNAs (LINC00478, PGM5-AS1, AL035610.1, MIR143HG, RP11-175K6.1, AC005550.4, and MIR497HG) have good single-factor diagnostic value for breast cancer. AC093850.2 has a prognostic value for breast cancer. AC005550.4 and MIR497HG can better distinguish breast cancer patients in early-stage from the advanced-stage. Low expression of MAGI2-AS3, LINC00478, AL035610.1, MIR143HG, and MIR145 may be associated with lymph node metastasis in breast cancer. Conclusion Our study provides candidate biomarkers for the diagnosis and prognosis of breast cancer, as well as a bioinformatics basis for the further elucidation of the molecular pathological mechanism of breast cancer.

scholarly journals Identification and Validation of a Predictive Immune-related Genes Signature for the Prognosis of Cholangiocarcinoma

2020 ◽  
Author(s):  
Rui Zhang ◽  
Chen Chen ◽  
Qi Li ◽  
Jialu Fu ◽  
Dong Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
High Risk ◽  
Risk Score ◽  
Risk Model ◽  
Predictive Accuracy ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Immune Related Genes

Abstract Background: Immune-related genes (IRGs) play a crucial role in the initiation and progression of cholangiocarcinoma (CCA). However, immune signatures have rarely been used to predict prognosis of CCA. The aim of this study was to construct a novel model for CCA to predict survival based on IRGs expression data.Methods: The gene expression profiles and clinical data of CCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were integrated to establish and validate prognostic IRG signatures. Differentially expressed immune-related genes were screened. Univariate and multivariate Cox analysis were performed to identify prognostic IRGs, and the risk model that predicts outcomes was constructed. Furthermore, receiver operating characteristic (ROC) and Kaplan-Meier curve were plotted to examine predictive accuracy of the model, and a nomogram was constructed based on IRGs signature, combining with other clinical characteristics. Finally, CIBERSORT was used to analyze the association of immune cells infiltration with risk score.Results: We identified that 223 IRGs were significantly dysregulated in patients with CCA, among which five IRGs (AVPR1B, CST4, TDGF1, RAET1E and IL9R) were identified as robust indicators for overall survival (OS), and a prognostic model was built based on the IRGs signature. Meanwhile, patients with high risk had worse OS in training and validation cohort, and the area under the ROC was 0.898 and 0.846, respectively. Nomogram demonstrated that immune risk score contributed much more points than other clinicopathological variables, with a C-index of 0.819 (95% CI, 0.727-0.911). Finally, we found that IRGs signature was positively correlated with the proportion of CD8+ T cells, neurophils and T gamma delta, while negatively with that of CD4+ memory resting T cells.Conclusions: We established and validated an effective five IRGs-based prediction model for CCA, which could accurately classify patients into groups with low and high risk of poor prognosis.

171 THE EFFECT OF TRICHOSTATIN A ON THE DEVELOPMENT AND THE GLOBAL GENE EXPRESSION PATTERNS IN MOUSE EMBRYOS DEVELOPING IN VITRO

2008 ◽  
Vol 20 (1) ◽  
pp. 165
Author(s):  
X. S. Cui ◽  
X. Y. Li ◽  
T. Kim ◽  
N.-H. Kim
Keyword(s):  
Gene Expression ◽  
Trichostatin A ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Mouse Embryos ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Cell Stage

Trichostatin A (TSA) is an inhibitor of histone deacetylase and is able to alter gene expression patterns by interfering with the removal of acetyl groups from histones. The aim of this study was to determine the effect of TSA treatment on the development and gene expression patterns of mouse zygotes developing in vitro. The addition of 100 nm TSA to the culture medium did not affect the cleavage of mouse embryos (TSA treatment, 148/150 (99%) v. control, 107/107 (100%)); however, embryos that were treated with TSA arrested at the 2-cell stage (145/148, 98%). We estimated the number of nuclei in control and TSA-treated embryos by propidium iodide staining, taking into account the presence of any cells with two or more nuclei. At 62–63 h post-hCG stimulation, control zygotes had developed to the 4-cell stage and exhibited one nucleus in each blastomere, indicative of normal development. In contrast, we observed tetraploid nuclei in at least one blastomere in 20.8% (11/53) of the embryos that had been treated with TSA. At 28–29 h post-hCG stimulation (metaphase of the 1-cell stage), there was no difference in the mitotic index (as determined by analyzing the microtubule configuration) in the TSA group compared to the control group. At the 2-cell stage, however, we did not observe mitotic spindles and metaphase chromatin in embryos in the TSA treatment group compared to the controls. Interestingly, when embryos were cultured in TSA-free medium from 35 h post-hCG stimulation (S- or early G2-phase of the 2-cell stage) onward, almost all of them (47/50) developed to the blastocyst stage. In contrast, when embryos were cultured in TSA-free medium from 42 h post-hCG stimulation (middle G2-phase of the 2-cell stage) onward, they did not develop to the 4-cell stage. We used Illumina microarray technology to analyze the gene expression profiles in control and TSA-treated late 2-cell-stage embryos. Applied Biosystems Expression System software was used to extract assay signals and assay signal-to-noise ratio values from the microarray images. Our data showed that 897 genes were significantly (P < 0.05; 2-sample t-test) up- or down-regulated by TSA treatment compared to controls. Analysis using the PANTHER classification system (https://panther.appliedbiosystems.com) revealed that the 575 genes that were differentially expressed in the TSA group compared to the control were classified as being associated with putative biological processes or molecular function. Overall, in terms of putative biological processes, more nucleoside, nucleotide, and nucleic acid metabolism, protein metabolism and modification, signal transduction, developmental process, and cell cycle genes were differentially expressed between the TSA and control groups. In terms of putative molecular function, more nucleic acid-binding transcription factor and transferase genes were differentially expressed between the groups. The results collectively suggest that inhibition of histone acetylation in mouse embryos affects gene expression profiles at the time of zygotic genome activation, and this subsequently affects further development.

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