Multi-scale genomic, transcriptomic and proteomic analysis of colorectal cancer cell lines to identify novel biomarkers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72296 | GEO | 2016/08/23
SECONDARY ACCESSION(S): PRJNA293684
REPOSITORIES: GEO
Similar Datasets
Project description:The objective of this study was to measure copy number alterations in a panel of 15 CRC cell lines and relate them to treatment sensitivity. Assessment of copy number variations in a panel of 15 colorectal cancer cell lines
2016-08-23 | E-GEOD-72296 | biostudies-arrayexpress
Project description:Selecting colorectal cancer (CRC) patients likely to respond to therapy remains a clinical challenge. The objectives of this study were to establish which genes were differentially expressed with respect to treatment sensitivity and relate this to copy number in a panel of 15 CRC cell lines. Copy number variations of the identified genes were assessed in a cohort of colorectal cancers. IC50’s were measured for 5-fluorouracil, oxaliplatin, and BEZ-235, a PI3K/mTOR inhibitor. Cell lines were profiled using array comparative genomic hybridisation, Illumina gene expression analysis, reverse phase protein arrays, and targeted sequencing of KRAS hotspot mutations.
2016-08-31 | GSE72544 | GEO
Project description:Selecting colorectal cancer (CRC) patients likely to respond to therapy remains a clinical challenge. The objectives of this study were to establish which genes were differentially expressed with respect to treatment sensitivity and relate this to copy number in a panel of 15 CRC cell lines. Copy number variations of the identified genes were assessed in a cohort of CRCs. IC50's were measured for 5-fluorouracil, oxaliplatin, and BEZ-235, a PI3K/mTOR inhibitor. Cell lines were profiled using array comparative genomic hybridisation, Illumina gene expression analysis, reverse phase protein arrays, and targeted sequencing of KRAS hotspot mutations. Frequent gains were observed at 2p, 3q, 5p, 7p, 7q, 8q, 12p, 13q, 14q, and 17q and losses at 2q, 3p, 5q, 8p, 9p, 9q, 14q, 18q, and 20p. Frequently gained regions contained EGFR, PIK3CA, MYC, SMO, TRIB1, FZD1, and BRCA2, while frequently lost regions contained FHIT and MACROD2. TRIB1 was selected for further study. Gene enrichment analysis showed that differentially expressed genes with respect to treatment response were involved in Wnt signalling, EGF receptor signalling, apoptosis, cell cycle, and angiogenesis. Stepwise integration of copy number and gene expression data yielded 47 candidate genes that were significantly correlated. PDCD6 was differentially expressed in all three treatment responses. Tissue microarrays were constructed for a cohort of 118 CRC patients and TRIB1 and MYC amplifications were measured using fluorescence in situ hybridisation. TRIB1 and MYC were amplified in 14.5% and 7.4% of the cohort, respectively, and these amplifications were significantly correlated (p≤0.0001). TRIB1 protein expression in the patient cohort was significantly correlated with pERK, Akt, and Caspase 3 expression. In conclusion, a set of candidate predictive biomarkers for 5-fluorouracil, oxaliplatin, and BEZ235 are described that warrant further study. Amplification of the putative oncogene TRIB1 has been described for the first time in a cohort of CRC patients.
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Project description:Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-scale DNA hypermethylation analysis technique using plasma is attractive for the noninvasive early detection of CRC. The methylated CpG tandems amplification and sequencing (MCTA-Seq) method was applied to plasma samples from 147 CRC patients and 134 controls in which 5 from the CRC patients and 2 from the control subjects failed to pass a quality control value and were excluded from further analysis. The capacity of the method for discriminating CRC and hepatocellular carcinoma (HCC) was assessed. We identified many DNA methylation markers including known (e.g., SEPT9 and IKZF1) and novel (e.g., EMBP1, KCNQ5 and CHST11) CpG islands for detecting CRC in blood. A panel of 80 markers significantly discriminated early stage CRC and controls with a sensitivity of 78% and a specificity of 90%. This method can efficiently distinguish between early stage CRC and HCC. MCTA-Seq is a promising method for the noninvasive detection of CRC that also shows great potential for identifying the tissue of origin of cancer.
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Project description:Colorectal cancer (CRC) shows the high mortality and morbidity. The mortal number of patients and the morbid number of patients with CRC is also increasing. However, the genes which relate to promote tumorigenesis in CRC remain unclear. In order to investigate specific genes and pathways involved in CRC tumorigenesis, we compared genes expressed between three dimensional cultures and control two-dimensional cultures. Total RNA was prepared from the CRC cell lines under the condition of two-dimensional culture and three dimensional culture.
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Project description:Colorectal cancer (CRC) shows the high mortality and morbidity. The mortal number of patients and the morbid number of patients with CRC is also increasing. However, the genes which relate to promote tumorigenesis in CRC remain unclear. In order to investigate specific genes and pathways involved in CRC tumorigenesis, we compared genes expressed between three dimensional cultures and control two-dimensional cultures.
2014-04-12 | GSE56738 | GEO
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