Mutational Analysis of Colorectal PDX models
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001001171 | EGA |
REPOSITORIES: EGA
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Project description:We established an in vivo model of organ-specific colorectal cancer metastasis and demonstrated that the CD110+ tumor initiating cells contribute for colorectal liver metastasis. To gain a deeper understanding of its metastatic capacity, we performed a genome-wide transcriptome analysis on the CD110+ tumor cells derived from primary colon xenografts and their matched liver metastases. Results provide important information of the responses of the CD110+ cells during the process of liver colonization. Total RNA obtained from the CD110+ cells sorted from primary colorectal tumors (CRC102-PT and CRC108-PT) compared to those from the corresponding liver metastases (CRC102-LM and CRC108-LM).
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Project description:We established an in vivo model of organ-specific colorectal cancer metastasis and demonstrated that the CD110+ tumor initiating cells contribute for colorectal liver metastasis. To gain a deeper understanding of its metastatic capacity, we performed a genome-wide transcriptome analysis on the CD110+ tumor cells derived from primary colon xenografts and their matched liver metastases. Results provide important information of the responses of the CD110+ cells during the process of liver colonization.
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Project description:Comparison of genomic alterations of primary colorectal cancers with liver metastases of the same patient Keywords: array CGH, colorectal cancer, colon cancer, liver metastasis 21 primary colorectal cancers and 21 matched liver metastases hybridized against sex-matched control pools
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Project description:Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. Keywords: gene expression profiling using cDNA microarray We performed 17K cDNA microarray with the amplified RNAs from the following tissue samples: normal colorectal mucosa, primary colorectal tumors, normal liver and liver metastasis tumors, and primary colorectal tumors without liver metastasis. Organ-specific genes in normal colon and liver tissues were excluded from the pre-filtered genes, and then we discovered and validated liver metastasis-specific genes commonly up-regulated in the primary colorectal tumors and liver metastasis tumors. To confirm the microarray data, we performed a RT-PCR of two genes (WNT5A and carbonic anhydrase II) in the primary colorectal tumors with and without liver metastases.
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Project description:About 50% of colorectal cancer patients develop liver metastases. Patients with metastatic colorectal cancer have 5-year survival rates below 20% despite new therapeutic regimens. Tumor heterogeneity has been linked with poor clinical outcome, but was so far mainly studied via bulk genomic analyses. In this study we performed spatial proteomics via MALDI mass spectrometry imaging on six patient matched CRC primary tumor and liver metastases to characterize interpatient, intertumor and intratumor hetereogeneity. We found several peptide features that were enriched in vital tumor areas of primary tumors and liver metastasis and tentatively derived from tumor cell specific proteins such as annexin A4 and prelamin A/C. Liver metastases of colorectal cancer showed higher heterogeneity between patients than primary tumors while within patients both entities show similar intratumor heterogeneity sometimes organized in zonal pattern. Together our findings give new insights into the spatial proteomic heterogeneity of primary CRC and patient matched liver metastases.
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Project description:Comparison of genomic alterations of primary colorectal cancers with liver metastases of the same patient Keywords: array CGH, colorectal cancer, colon cancer, liver metastasis
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Project description:The purpose of this study is to identify miRNAs involved in the pathology of colorectal cancer (CRC) liver metastasis and investigate their underlying mechanisms. A total of 39 miRNAs were identified to be differentially expressed between 16 primary CRC tissues with liver metastases and 16 CRC tissues without liver metastases from 32 patients by Affymetric miRNA microarrays. 16 coloretcal cancer tissues with liver metastasis and 16 colorectal cancer tissues without liver metastasis were included in this study for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify the differentially expressed miRNAs between colorectal cancer tissues with and without liver metastasis.
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