Project description:The aim of this study is to identify prognostic gene expression signatures associated with two molecularly distinct subtypes of colorectal cancer. Samples were taken from colorectal cancers in surgically resected specimens in 96 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. This is a test set for validation of prognostic gene expression signature that was developed from GSE14333. All data were normalized by using the RMA method (affy package in R/Bioconductor).
Project description:Clinical heterogeneity of gastric cancer reflected in unequal outcome of treatment is poorly defined in molecular level, and molecular subtypes and their associated biomarkers have not been established to improve prognostification and treatment of gastric cancer. Using microarray technologies, we analyzed gene expression profiling data from patients with advanced gastric cancer and uncovered potential prognostic subtypes and identify gene expression signature associated with prognosis. Using microarray technologies, we analyzed gene expression profiling data from patients with advanced gastric cancer and uncovered potential prognostic subtypes and identify gene expression signature associated with prognosis.
Project description:Colorectal cancer molecular signatures derived from omics data can be employed to stratify CRC patients and aid decisions about therapies or evaluate prognostic outcome. However, molecular biomarkers for identification of patients at increased risk of disease relapse are currently lacking. Here, we present a comprehensive multi-omics analysis of a Danish colorectal cancer tumor cohort composed of 412 biopsies from tumors of 371 patients diagnosed at TNM stage II or III. From mass spectrometry-based patient proteome profiles, we classified the tumors into four molecular subtypes, including a mesenchymal-like subtype. As the mesenchymal-rich tumors are known to represent the most invasive and metastatic phenotype, we focused on the protein signature defining this subtype to evaluate their potential as relapse risk markers. Among signature-specific proteins, we followed-up Caveolae-Associated Protein-1 (CAVIN1) and demonstrated its role in tumor progression in a 3D in vitro model of colorectal cancer. Compared to previous omics analyses of CRC, our multi-omics classification provided deeper insights into EMT in cancer cells with stronger correlations with risk of relapse.
Project description:Integrated analyses reveal two molecularly and clinically distinct subtypes of H3 K27M-mutant diffuse midline gliomas with prognostic significance
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:Tumor-derived extracellular vesicles (TEVs) play a crucial role in cancer progression, metastasis and therapy resistance but their distinct profiles across different cancer stages and molecular subtypes remain underexplored. This study analyzed TEVs from epithelial (CMS2) and mesenchymal (CMS4) subtypes of colorectal cancer (CRC) using six cell lines and clinical samples. Investigation of the cargo of vesicles secreted by the two subtypes revealed significant differences in mRNA, miRNA, and protein profiles between the two subtypes. Notably, CMS2 predominantly secreted smaller, Tetraspanin-8 (TSPAN8) enriched EVs, while CMS4 produced both larger and smaller EVs, enriched in TSPAN4. This underscores the complexity of vesicle heterogeneity between these subtypes. Additionally, we assessed miRNA profiles from plasma-derived bulk TEVs in CRC patients. Our integrative analysis identified a distinct miRNA signature specific to each subtype, indicating that TEVs from CMS2 and CMS4 cells can be detected in circulation and may serve as potential diagnostic tool for CRC.
Project description:Tumor-derived extracellular vesicles (TEVs) play a crucial role in cancer progression, metastasis and therapy resistance but their distinct profiles across different cancer stages and molecular subtypes remain underexplored. This study analyzed TEVs from epithelial (CMS2) and mesenchymal (CMS4) subtypes of colorectal cancer (CRC) using six cell lines and clinical samples. Investigation of the cargo of vesicles secreted by the two subtypes revealed significant differences in mRNA, miRNA, and protein profiles between the two subtypes. Notably, CMS2 predominantly secreted smaller, Tetraspanin-8 (TSPAN8) enriched EVs, while CMS4 produced both larger and smaller EVs, enriched in TSPAN4. This underscores the complexity of vesicle heterogeneity between these subtypes. Additionally, we assessed miRNA profiles from plasma-derived bulk TEVs in CRC patients. Our integrative analysis identified a distinct miRNA signature specific to each subtype, indicating that TEVs from CMS2 and CMS4 cells can be detected in circulation and may serve as potential diagnostic tool for CRC.