Project description:(Purpose) Biological classification of colorectal cancer (CRC) can help to understand its heterogeneous background. The purpose of this study is to classify CRC based on gene expression profiles using formalin-fixed paraffin-embedded (FFPE) samples and to correlate subgroups of CRC with biological features and clinical outcomes. (Results) CRC was clustered into four subgroups by unsupervised hierarchical clustering method. These subgroups show different biological and clinical features. (Conclusion) Gene expression profiles of CRC using FFPE samples distinguish four subgroups that had different biological features and clinical outcomes. These subgroups may explain heterogeneity of CRC and be useful biomarker for clinical.
Project description:(Purpose) Biological classification of colorectal cancer (CRC) can help to understand its heterogeneous background. The purpose of this study is to classify CRC based on gene expression profiles using formalin-fixed paraffin-embedded (FFPE) samples and to correlate subgroups of CRC with biological features and clinical outcomes. (Results) CRC was clustered into four subgroups by unsupervised hierarchical clustering method. These subgroups show different biological and clinical features. (Conclusion) Gene expression profiles of CRC using FFPE samples distinguish four subgroups that had different biological features and clinical outcomes. These subgroups may explain heterogeneity of CRC and be useful biomarker for clinical. Patients and Methods: One hundred patients with unresectable and advanced or recurrent CRC who underwent the surgical resection from 1998 to 2010 were enrolled in this study. RNA extracted from FFPE samples was subjected to gene expression microarray. After comprehensive gene expression analysis, CRC were classified by an unsupervised hierarchical clustering and a principle component analysis (PCA). Mutation analysis of KRAS, BRAF, PIK3CA and TP53 genes were performed by direct DNA sequencing. Correlation between the biological information, clinicopathological factors and clinical outcomes were analyzed.
Project description:To characterize DNA methylation-based subgroups in colorectal cancer, we performed genome-scale DNA methylation profiling of 125 colorectal tumor samples and 29 histologically normal-adjacent colonic tissue samples using the Illumina Infinium DNA methylation assay, which assesses the DNA methylation status of 27,578 CpG sites located at the promoter regions of 14,495 protein-coding genes. We identified four DNA methylation-based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic and clinical features, indicating that they represent biologically distinct subgroups.
Project description:To characterize DNA methylation-based subgroups in colorectal cancer, we performed genome-scale DNA methylation profiling of 125 colorectal tumor samples and 29 histologically normal-adjacent colonic tissue samples using the Illumina Infinium DNA methylation assay, which assesses the DNA methylation status of 27,578 CpG sites located at the promoter regions of 14,495 protein-coding genes. We identified four DNA methylation-based subgroups of CRC using model-based cluster analyses. Each subtype shows characteristic genetic and clinical features, indicating that they represent biologically distinct subgroups. Bisulfite converted DNA from fresh frozen 125 colorectal tumors and 29 adjacent normal tissues were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2
Project description:Identification of novel molecular subgroups Background: International consensus recognises four medulloblastoma molecular subgroups - WNT, SHH, Group 3 and Group 4 - each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. Subgroups harbor distinct clinico-pathological and molecular features, underpin current disease sub-classification and initial subgroup-directed therapies are underway in clinical trials (i.e. reduced risk-adapted treatments for favorable-risk WNT patients; SMO inhibitors for SHH patients). However, significant biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved. Methods: We undertook comprehensive molecular profiling and unsupervised class discovery (non-negative matrix factorization, t-SNE) of test and validation cohorts to identify consensus primary molecular subgroups within childhood medulloblastoma (<16.0 years), and characterize their clinical and biological significance. Survival modeling was performed in clinically-annotated centrally-reviewed patients (>3.0 years). Findings: Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified, characterized by distinct biological/clinical features. For instance, SHH comprised two age-dependent subgroups, while Grp3 and Grp4 each split into two subgroups with significantly different survival rates. Survival analysis identified secondary features predictive of outcome. Cross-validated subgroup-dependent models incorporating these novel subgroups along with secondary features and established disease risk-factors, outperformed current disease risk-stratification schemes. These schema stratified patients into four clinical risk-groups - favorable-risk (91% 5-year survival, 25% of patients), standard-risk (81%, 23%), high-risk (42%, 38%) and very high-risk (28%, 13%) - to be considered for treatment reduction, intensification or novel therapies respectively. Interpretation: The discovery of seven novel, clinically-significant, subgroups significantly improves disease risk-stratification and provides a new foundation for future research and clinical investigations.
Project description:Recent work built on published transcriptional subtypes of colorectal cancer (CRC) has shown that tumor stromal content impacts CRC classification, with both clinical and biological implications. To Tackle the issue of intrinsic epithelial gene profiles, we assembled a dataset of matched liver metastatic colorectal cancer and Patients Derived Xenografts. in which the stroma of the original tumor is substituted by murine tissue, we deployed a molecularly annotated collection of 515 PDXs from 244 patients as a resource for species (human)-specific assessment of cancer-cell intrinsic transcriptional features. We identified five ColoRectal cancer Intrinsic Subtypes (CRIS) endowed with functional and phenotypic characteristics related to specific genetic traits, most of which were not evidenced in the transcriptional subgroups reported in previous studies.
Project description:Recent work built on published transcriptional subtypes of colorectal cancer (CRC) has shown that tumor stromal content impacts CRC classification, with both clinical and biological implications. To Tackle the issue of intrinsic epithelial gene profiles, we assembled a dataset of matched liver metastatic colorectal cancer and Patients Derived Xenografts. in which the stroma of the original tumor is substituted by murine tissue, we deployed a molecularly annotated collection of 515 PDXs from 244 patients as a resource for species (human)-specific assessment of cancer-cell intrinsic transcriptional features. We identified five ColoRectal cancer Intrinsic Subtypes (CRIS) endowed with functional and phenotypic characteristics related to specific genetic traits, most of which were not evidenced in the transcriptional subgroups reported in previous studies.
Project description:Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features
Project description:Generally, cancer tissue is palpated as a hard mass. On the other hand, it is not clear the nature of elasticity in cancer tissue. The aim in this study is to evaluate clinical utility of measuring elastic module in colorectal cancer tissue. Using a tactile sensor, we measured the elastic module of 106 surgically resected colorectal cancer tissues. The data of the elastic module were compared with the clinicopathological findings including stromal features represented by azan and α-SMA positive area ratio in tumor area. Finally cDNA microarray profile of the tumor with high elastic module was compared with that with low elastic module Higher elastic module in tumor was associated with pathological T-, N- and M-Stage (p < 0.001, p = 0.001 and p = 0.011, respectively). Patients with high elastic module showed shorter disease free survival than patients with low elastic module. The elastic module showed strongly positive correlation with azan positive area ratio (r = 0.908) and α-SMA positive area ratio (r = 0.921). Finally, the cDNA microarray data of the tumor with high elastic module revealed distinct gene expression profile from that with low elastic module. Assessment of elasticity of colorectal cancer tissue can be available for more accurate clinical stage or prognosis estimation. Distinct phenotypical feature of the high elastic module tumor and their strong association with stromal feature seemed to be suggesting the existence of biological mechanism involved in this phenomenon, which may contribute to the future therapy. We selected four samples from the highest and the lowest EM with RIN > 6.0 measured with a 2100 Bioanalyzer (Aligent Tochnologies, Santa Clara, CA, USA) and with stage II (pTNM pathologic classification). We excluded one sample in each group because of high GAPDH.