Project description:Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters for identification of high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, are established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not been investigated for this specific group of patients. The aim of the present study is to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer. Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples where hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction Results: Patients with stage II colon cancer who had relapse of disease showed significant more losses on chromosome 4, 5, 15q, 17q and 18q. When microsatellite stable (MSS) patients were analyzed separately, only losses on chromosome 4q22.1-4q35.2 predicted worse outcome in stage II colon cancer patients. No differences in clinicopathological characteristics between patients with and without relapse were observed. Conclusion: Losses on 4q22.1-4q35.2 predict worse outcome in MSS stage II colon cancer patients and may aid in the selection of patients for adjuvant therapy.
Project description:Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters for identification of high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, are established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not been investigated for this specific group of patients. The aim of the present study is to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer. Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples where hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction Results: Patients with stage II colon cancer who had relapse of disease showed significant more losses on chromosome 4, 5, 15q, 17q and 18q. When microsatellite stable (MSS) patients were analyzed separately, only losses on chromosome 4q22.1-4q35.2 predicted worse outcome in stage II colon cancer patients. No differences in clinicopathological characteristics between patients with and without relapse were observed. Conclusion: Losses on 4q22.1-4q35.2 predict worse outcome in MSS stage II colon cancer patients and may aid in the selection of patients for adjuvant therapy. 40 Stage II colorectal cancer (CRC) tissue samples (FFPE), 16 with and 24 without relapse of tumor
Project description:Genome wide miRNA expression profiling was performed using Affymetric miRNA v. 3.0 Array on 48 samples which included paired FFPE colon tuomor and metastisized liver and paired normal colon, normal liver). The data set was divided into two categories and identified by tissue source and patient demographics: Tissue (Colon, Liver), Source (Colon Tumor Liver Met, Colon Normal, Liver Normal), Sex (Male, Female), Patient Pair. microRNAs (miRs) are frequently dysregulated in colorectal cancer (CRC) and subsets are correlated with advanced tumor stage and metastasis. Despite this, the development of prognostic biomarkers that predict metastatic potential remain limited. Our study was designed to identify, validate, and elucidate underlying biology imposed by a miR signature that defines and predicts metastatic disease. Genome-wide miR expression profiling was performed on fourteen patient-matched stage IV primary CRC tumors and corresponding liver metastases using microRNA array technology. Based on these results, this miR panel was then validated and evaluated in normal colon tissue (N = 5), early stage (I & II, N = 11) and late stage (Stage III & IV, N = 14) colorectal primary tumors via qRT-PCR.