Project description:Analysis of microRNA expression of tumoral and non-tumoral colonic tissues. The aim of this study was to analyze the global miRNA signatures in various groups of well-characterized CRCs based on the presence of microsatellite instability (MSI).
Project description:Analysis of microRNA expression of tumoral and non-tumoral colonic tissues. The aim of this study was to analyze the global miRNA signatures in various groups of well-characterized CRCs based on the presence of microsatellite instability (MSI). Total RNA from formalin-fixed paraffin-embedded tissue blocks from 4 different groups (normal colonic mucosa, Lynch syndrome tumors, sporadic MSI tumors and MSS tumors) was isolated using the RecoverAll Total Nucleic Acid Isolation Kit (Ambion) according to manufacturer instructions. MiRNA expression profiles were analyzed using miRNA microarray platform.
Project description:Background. Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome. Results. We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response. Conclusions. This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.
Project description:In this study, we aimed to identify the different histopathological features of tumors with microsatellite instability (MSI) compared to microsatellite stable (MSS) in patients who underwent surgery for colorectal cancer. We also planned to determine how MSI affects prognostic parameters.
Project description:Approximately 15% of colorectal cancer (CRC) patients present with high levels of microsatellite instability (MSI-H), which is driven by defective mismatch repair (dMMR). While about 20% of MSI-H tumors are associated with the hereditary condition, Lynch syndrome (LS), the majority develop through non-hereditary mechanisms. In recent years, the molecular processes underpinning tumor development in LS patients has been debated, with the longstanding view that dMMR is a secondary process in CRC development of LS patients being questioned. Here, we performed the first multi-omic analysis of normal colon organoids developed from LS and healthy patients to address questions regarding the development of dMMR in LS colon epithelial cells from cancer-free individuals.
Project description:Approximately 15% of colorectal cancer (CRC) patients present with high levels of microsatellite instability (MSI-H), which is driven by defective mismatch repair (dMMR). While about 20% of MSI-H tumors are associated with the hereditary condition, Lynch syndrome (LS), the majority develop through non-hereditary mechanisms. In recent years, the molecular processes underpinning tumor development in LS patients has been debated, with the longstanding view that dMMR is a secondary process in CRC development of LS patients being questioned. Here, we performed the first multi-omic analysis of normal colon organoids developed from LS and healthy patients to address questions regarding the development of dMMR in LS colon epithelial cells from cancer-free individuals.