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Effects of gene expression pattern and RAS/BRAF mutations on the course of colorectal cancer

ABSTRACT: Background and study aims Colorectal cancer, otherwise known as bowel cancer, is a disease where cancerous tumors develop in the large bowel (colon cancer) and cancer of the back passage (rectal cancer). Currently, histological characteristics of the tumor (i.e. its structure) and whether there are mutations to the KRAS or BRAF genes are used to predict the likely clinical course of colorectal cancer (i.e. the prognosis). Analysis of the expression profile of the tumor (a test that identifies which genes have been mutated) can increase the prognostic significance of molecular characteristics (distinguishing features of the individual cancer cells) for colorectal cancer. The aim of this study is to find out how well this new technology can help in the prognosis of this disease. Who can participate? Adults with potentially curable colorectal cancer that have not had chemotherapy and/or radiotherapy before surgery. What does the study involve? Tumors that have been removed from patients though surgery have their expression profile analysed. After this analysis, they are assigned to one of five different subtypes, including, stem-like, inflammatory, transit-amplifying, goblet-like and enterocyte. Patients with stage 1 cancer are then followed up three years after the surgery. Patients with stage III-IV are treated with chemotherapy according to common oncological practice. Patients with stage II receive either chemotherapy or not depending upon the decision of a chemotherapist. Follow up for all patients in the study is 3 years after surgery to see how long they survived disease free, how long it took them to relapse (if they did so) and how long did they survive for after surgery.

DISEASE(S): Colorectal Cancer

PROVIDER: 2413028 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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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.

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Effects of gene expression pattern and RAS/BRAF mutations on the course of colorectal cancer

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