Project description:D122p53 mice (a model of D133p53 isoform) are tumour prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed ∆122p53 mice with IL-6 deficient mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence, and metastasis. We also show that D122p53 activates RhoA-ROCK signalling leading to tumour cell invasion which is IL-6 dependent and can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we show that Δ133p53 activates the these pathways, resulting in invasive and migratory phenotypes, in colorectal cancer cells. Gene expression analysis of colorectal tumours showed enrichment of GPCR signalling associated with D133TP53 mRNA. Patients with elevated D133TP53 mRNA levels had a shorter disease free survival. Our results suggest that D133p53 promotes tumour invasion by activation of the JAK-STAT and RhoA-ROCK pathways and that patients whose tumours have high D133p53 may benefit from therapies targeting these pathways. In this dataset, we included the gene expression data from 35 colorectal cancers. These data were used to identify a list of enriched genesets associated with D133TP53 mRNA expression in colorectal tumours
Project description:Wiskott-Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis. We used microarrays for the validation of a WIPF1 co-expression module which was developed on two publically available datasets. Keywords: disease state analysis For the generation of our own microarray data set, 62 CRC patients undergoing elective standard oncological resection at the Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité, were prospectively recruited.
Project description:Wiskott-Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis. We used microarrays for the validation of a WIPF1 co-expression module which was developed on two publically available datasets. Keywords: disease state analysis
Project description:Samples were taken from colorectal cancers in surgically resected specimens in 155 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. Our MSI/MSS classifier was applied to these samples. Keywords: Expression profiling by array
Project description:Samples were taken from colorectal cancers in surgically resected specimens from 74 patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. Our MSI/MSS classifer was applied to these samples. Keywords: Expression profiling by array
Project description:Samples were taken from colorectal cancers in surgically resected specimens in 290 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. The training set of our prognosis classifier included the stage A and D samples. Validation used our stage B and C samples. Keywords: Expression profiling by array
Project description:Comparison of expression profiles of primary colorectal cancers with liver metastases of the same patient. Additionally, expression data of normal colon and liver tissue. Abstract of publication will be included upon publication Keywords: expression profiling, colorectal cancer, colon cancer, liver metastasis, normal colonic tissue, normal liver tissue RNA of 18 primary colorectal cancers, 18 matched liver metastases, 7 normal colon epithelium samples and 5 normal liver tissue samples hybridized on Human Sentrix-6 V2 (Illumina)
Project description:We stratified colorectal tumor samples using a new unsupervised, iterative method based on non-negative matrix factorization (NMF). The resulting five subtypes exhibited activation of specific signaling pathways, and significant differences in microsatellite status and tumor location. We could also align three CRC cell lines panels to these subtypes. mRNA from 62 colorectal tumor samples was hybridized to Affymetrix HGU133 Plus 2.0 expression arrays. Log2 gene expression values were calculated using RMA.
Project description:Comparison of expression profiles of primary colorectal cancers with liver metastases of the same patient. Additionally, expression data of normal colon and liver tissue. Abstract of publication will be included upon publication Keywords: expression profiling, colorectal cancer, colon cancer, liver metastasis, normal colonic tissue, normal liver tissue
Project description:Gene expression was analyzed in terms of canonical molecular changes and clinicopathological features to elucidate alternative or subordinate pathways during colorectal tumorigenesis and tumor growth. Eighty-four sporadic colorectal cancer patients, standardized by tumor location, were consecutively enrolled. Representative molecular changes including APC, TP53, Wnt, RAF, and mismatch repair defect (MMR) were recorded for each sample. Keywords: disease state analysis; sub-type analysis within colorectal cancers