Early and advanced gastric cancer genomes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE57176 | GEO | 2014/06/30
SECONDARY ACCESSION(S): PRJNA245831
REPOSITORIES: GEO
Similar Datasets
Project description:Early gastric cancers (EGC) precede advanced gastric cancers (AGC) with a favorable clinical outcome compared to advanced gastric cancers (AGC). To understand the progression mechanisms of EGC to AGC, it is required to disclose the EGC and AGC genomes in terms of the the mutational and evolutionary perspectives. In this study, we performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (5 EGC and 4 AGC) and eight MS-stable (MSS) gastric cancers (4 EGC and 4 AGC). Unexpectedly, we observed no substantial differences in the number, sequence composition and functional consequences (potential driver mutations and affected pathways) of the mutations and CNAs between EGC and AGC genomes in both MSI-H and MSS cases. Gastrectomy tissues from 17 GC patients were used for this study. The hospital pathology department confirmed pathologic features of the GC (e.g., EGC vs. AGC, differentiation, lymph node metastasis and TNM stage). All of the picked areas from tumor and normal areas were frozen, cut, and stained with hematoxylin & eosin (H&E). Two pathologists selected cases with rich tumor cell population (at least 60%), which were subsequently used in the study. Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol.
2014-06-30 | E-GEOD-57176 | biostudies-arrayexpress
Project description:Methylation profiling in gastric cancer : normal serum vs Early and Advanced cancer serum Direct comparison experiment : Normal vs EGC, Normal vs AGC
2012-08-17 | E-GEOD-39532 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) may contribute to tumorigenesis and cancer progression by regulating the gene in various cancers, including advanced gastric cancer (AGC). To investigate differentially expressed lncRNAs in AGC, we use whole transcriptome sequencing in 3 pairs of human gastric adenocarcinoma and the corresponding normal tissues.
2023-08-10 | GSE210909 | GEO
Project description:Samples were taken from colorectal cancers in surgically resected specimens in 84 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes between MSI and MSS cancers and, furthermore, to determine the distinct characteristics of proximal and distal MSI cancers. Experiment Overall Design: Eighty-four colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. To identify molecular signatures of MSI cancers, gene expression profiles were compared between MSI and MSS cancers. Next, we examined the difference in gene expression profiles between proximal and distal MSI cancers.
2008-06-13 | E-GEOD-4554 | biostudies-arrayexpress
Project description:Gastric cancer (GC) is the world's third leading cause of cancer mortality. In spite of significant therapeutic improvement, the clinical outcome for patients with advanced GC is poor; thus, the identification and validation of novel targets is extremely important from a clinical point of view. We generated a wide, multi-level platform of GC models, comprising 100 Patient-derived xenografts (PDXs), primary cell lines and organoids. Samples were classified according to their histology, microsatellite stability (MS) and Epstein-Barr virus status, and molecular profile. This PDX platform is the widest in an academic institution and it includes all the GC histologic and molecular types identified by TCGA. PDX histopathological features were consistent with those of patients’ primary tumors and were maintained throughout passages in mice. Factors modulating grafting rate were histology, TNM stage, copy number variation of tyrosine kinases/KRAS genes and MSI status. PDX and PDX-derived cells/organoids demonstrated potential usefulness to study targeted therapy response. Finally, PDX transcriptomic analysis identified a cancer cell intrinsic MSI signature, which was efficiently exported to gastric cancer, allowing the identification -among MSS patients- of a subset of MSI-like tumors with common molecular assets and significant better prognosis. We generated a wide gastric cancer PDX platform, whose exploitation will help identify and validate novel 'druggable' targets and define the best therapeutic strategies. Moreover, transcriptomic analysis of GC PDXs allowed the identification of a cancer cell intrinsic MSI signature, recognizing a subset of MSS patients with MSI transcriptional traits, endowed with better prognosis.
2019-10-15 | GSE128459 | GEO
Project description:Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed. Unsupervised analysis showed that the immune and apoptotic gene networks efficiently discriminated these two cancer types. Hierarchical clustering analysis revealed numerous gene expression changes associated with the MSI phenotype. Amongst these, the p53-responsive genes maspin and 14-3-3 sigma were significantly more expressed in tumours with than without MSI. A tight immunosurveillance coupled with a functional p53 gene response is consistent with the better prognosis of MSI cancers. Frequent silencing of MLH1 and downregulation of MMR target genes, such as MRE11 and MBD4, characterised MSI tumours. The downregulation of SMUG1 was also a typical feature of these tumours. The DNA repair gene expression profile of gastric cancer with MSI is of relevance for therapy response. Experiment Overall Design: Genes differentially expressed between MSI and MSS tumours were identified as follows: (i) gene probe sets were pre-selected for being flagged as ‘PRESENT’ in at least 10 tumour samples (21,324 probe sets); (ii) the probe set signal values on the pre-selected probe sets were used to run a t-test between the two types of tumour samples; (iii) the false discovery rate (FDR) method was applied to the t-test calculated p-values to correct for multiple testing and (iv) a false discovery rate <0.05 and a t-test p-value < 0.01 were chosen as threshold criteria to identify the genes differentially expressed in tumours with and without MSI
2009-01-03 | E-GEOD-13911 | biostudies-arrayexpress
Project description:We compared the expression of genes related to inflammatory cytotoxic functions between MSI and MSS (HLA class I negative and positive) gastrointestinal adenocarcinomas (GIACs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two GIACs were divided into three study groups as a function of HLA class I expression and MSI phenotype. Comparison between eight high-level MSI (MSI-H) and 8 MSS/HLA+ (control) cancers identified 2170 differentially expressed genes (p< 0.05) after microarray analysis on the Affymetrix HG-U133-Plus-PM plate. We grouped genes in Gene Ontology functional categories: apoptotic programme (119 genes, p=5.1·10-7), leukocyte activation (32 genes, p=0.01), T cell activation (20 genes, p= 0.01), and cytokine production (19 genes, p= 0.04). Real-time RT-PCR and immunohistochemical evaluation were used to confirm some microarray data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+ T lymphocytes in the MSI-H group (p<0.001). Finally, tumours with immunohistochemical HLA class I negative pattern were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-ABC negative CRCs. In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumours, MSI/HLA- and MSS/HLA-, showed marked differences in the composition and intensity of infiltrating leukocytes, suggesting that their immune escape strategies involve distinct pathways. Case-control study. Samples were selected according to immunological criteria: those with total loss of HLA antigens and those without alterations in the expression of HLA molecules. In addition, the microsatellite instability genotype of all the samples was also analyzed, resulting in microsatellite stability (MSS) and microsatellite instability (MSI) samples. Therefore, three groups of samples were selected: MSS/HLA+, MSS/HLA-, and MSI. The MSS/HLA+ group was used as the control.
2011-02-28 | E-GEOD-27544 | biostudies-arrayexpress
Project description:Background. Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome. Results. We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response. Conclusions. This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.
2007-09-07 | E-TABM-326 | biostudies-arrayexpress
Project description:We compared the expression of genes related to inflammatory cytotoxic functions between MSI and MSS (HLA class I negative and positive) gastrointestinal adenocarcinomas (GIACs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two GIACs were divided into three study groups as a function of HLA class I expression and MSI phenotype. Comparison between eight high-level MSI (MSI-H) and 8 MSS/HLA+ (control) cancers identified 2170 differentially expressed genes (p< 0.05) after microarray analysis on the Affymetrix HG-U133-Plus-PM plate. We grouped genes in Gene Ontology functional categories: apoptotic programme (119 genes, p=5.1·10-7), leukocyte activation (32 genes, p=0.01), T cell activation (20 genes, p= 0.01), and cytokine production (19 genes, p= 0.04). Real-time RT-PCR and immunohistochemical evaluation were used to confirm some microarray data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+ T lymphocytes in the MSI-H group (p<0.001). Finally, tumours with immunohistochemical HLA class I negative pattern were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-ABC negative CRCs. In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumours, MSI/HLA- and MSS/HLA-, showed marked differences in the composition and intensity of infiltrating leukocytes, suggesting that their immune escape strategies involve distinct pathways.
2011-02-28 | GSE27544 | GEO
Project description:Samples were taken from colorectal cancers in surgically resected specimens in 84 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes between MSI and MSS cancers and, furthermore, to determine the distinct characteristics of proximal and distal MSI cancers. Keywords: repeat
2006-10-17 | GSE4554 | GEO