Four subgroups by gene expression profile correlate with biological and clinical features in colorectal cancer.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33193 | GEO | 2014/01/01
SECONDARY ACCESSION(S): PRJNA149243
REPOSITORIES: GEO
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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.
2014-01-01 | E-GEOD-33193 | biostudies-arrayexpress
Project description:This study reports clinical, genetic, epigenetic, gene expression, and cellular features distinguishing meningioma DNA methylation subgroups within meningioma DNA methylation groups. We present these data in the context of molecular and clinical models predicting postoperative outcomes across 565 meningiomas with comprehensive clinical follow-up from independent discovery and validation institutions. By discovering meningioma DNA methylation subgroups within meningioma DNA methylation groups, we provide an opportunity to resolve inconsistencies in the recent literature. In doing so, our study establishes an architecture that unifies opposing biological theories for the most common primary intracranial tumor
2022-10-10 | GSE212666 | GEO
Project description:Defining molecular features that can predict the recurrence of colorectal cancer (CRC) for stage II-III patients remains challenging in cancer research. Most available clinical samples are Formalin-Fixed and Paraffin-Embedded (FFPE). NanoString nCounter® and Affymetrix GeneChip® Human Transcriptome Array 2.0 (HTA) are the two platforms marketed for high-throughput gene expression profiling for FFPE tissue samples. In this study, to identify an optimal platform for the gene expression profiling of FFPE CRC samples, we evaluated the expression of 516 genes from published frozen tissue-derived prognostic signatures in 42 CRC patient samples measured by these two platforms. Based on HTA platform-derived data, we identified both gene (99 individual genes, FDR < 0.05) and gene set (four of the six reported multi-gene signatures with sufficient information for evaluation, P < 0.05) expression differences associated with survival outcomes. Using nCounter platform-derived data, only one of the six multi-gene signatures (P < 0.05) but no individual gene was associated with survival outcomes. Therefore, the HTA appears to provide a more robust gene expression dataset using genes from published gene signatures. Our study indicated that sufficiently high quality RNA could be obtained from FFPE tumor tissues to detect frozen tissue-derived prognostic gene expression signatures for CRC patients.
2016-08-31 | GSE78248 | GEO
Project description:Four subgroups by gene expression profile correlate with biological and clinical features in colorectal cancer.
| PRJNA149243 | ENA
Project description:Colorectal cancer (CRC) is a highly malignant solid tumor and causes millions of cancer related death worldwide. Here, using H3K27ac chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with gene expression data (RNA-seq), we describe the active cis-regulatory landscape across more than seventy diverse CRC patient tissues, including tumor and native tissue. Analysis of the enhancers and super-enhancers with recurrently gained or lost activity revealed novel, clinically relevant insights into CRC biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors which is responsible for tumorigenesis and the maintenance of normal intestinal function. Genomic studies have revealed four distinct consensus molecular subgroups (CMS) with divergent biology and clinical behavior and we reveal that differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity. Our integrated analysis of enhancer elements in a large series of CRC patient paired samples reveals novel insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins.
2021-08-26 | GSE156613 | GEO
Project description:Colorectal cancer (CRC) is a highly malignant solid tumor and causes millions of cancer related death worldwide. Here, using H3K27ac chromatin immunoprecipitation followed by sequencing (ChIP-seq) coupled with gene expression data (RNA-seq), we describe the active cis-regulatory landscape across more than seventy diverse CRC patient tissues, including tumor and native tissue. Analysis of the enhancers and super-enhancers with recurrently gained or lost activity revealed novel, clinically relevant insights into CRC biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors which is responsible for tumorigenesis and the maintenance of normal intestinal function. Genomic studies have revealed four distinct consensus molecular subgroups (CMS) with divergent biology and clinical behavior and we reveal that differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity. Our integrated analysis of enhancer elements in a large series of CRC patient paired samples reveals novel insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins.
2021-08-26 | GSE156451 | GEO
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.
2011-06-03 | GSE25062 | GEO
Project description:Background. Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. Methods. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Results. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. Conclusions. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome.
2018-06-26 | GSE116028 | GEO
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.
2017-05-29 | GSE93646 | GEO
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
2011-06-03 | E-GEOD-25062 | biostudies-arrayexpress