Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [CGH]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE40966 | GEO | 2013/05/22
SECONDARY ACCESSION(S): PRJNA175450
REPOSITORIES: GEO
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Project description:From a clinical and molecular perspective, colon cancer (CC) is a heterogeneous disease but to date no classification based on high-density transcriptome data has been established. The aim of this study was to build up a robust molecular classification of mRNA expression profiles (Affymetrix U133Plus2) of a large series of 443 CC and to validate it on an independent serie of 123 CC and 906 public dataset. We identified and validated six molecular subtypes in this large cohort as a combination of multiple molecular processes that complement current disease stratification based on clinicopathological variables and molecular markers. The biological relevance of these subtypes was consolidated by significant differences in survival. These insights open new perspectives for improving prognostic models and targeted therapies. Among a large series of colon cancers collected for the Cartes d'Identité des Tumeurs (CIT) program from the French Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net), 566 were analyzed for mRNA expression profiles using Affymetrix U133plus2 chip and, among theses, 463 could also be analyzed for DNA alteration profiles using the CGH Array ( CIT-CGHarray V6). The 566 tumors was divided into a discovery dataset of 443 CC and a validation dataset of 123 CC.
2013-05-22 | E-GEOD-39582 | biostudies-arrayexpress
Project description:From a clinical and molecular perspective, colon cancer (CC) is a heterogeneous disease but to date no classification based on high-density transcriptome data has been established. The aim of this study was to build up a robust molecular classification of mRNA expression profiles (Affymetrix U133Plus2) of a large series of 443 CC and to validate it on an independent serie of 123 CC and 906 public dataset. We identified and validated six molecular subtypes in this large cohort as a combination of multiple molecular processes that complement current disease stratification based on clinicopathological variables and molecular markers. The biological relevance of these subtypes was consolidated by significant differences in survival. These insights open new perspectives for improving prognostic models and targeted therapies. Among a large series of colon cancers collected for the Cartes d'Identité des Tumeurs (CIT) program from the French Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net), 566 were analyzed for mRNA expression profiles using Affymetrix U133plus2 chip and, among theses, 463 could also be analyzed for DNA alteration profiles using the CGH Array ( CIT-CGHarray V6). The 566 tumors was divided into a discovery dataset of 443 CC and a validation dataset of 123 CC.
2013-05-22 | E-GEOD-40966 | biostudies-arrayexpress
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Project description:Even though urothelial cancer (UC) is the fourth common tumor type among males, progress in treatment development has been deficient. Pathological assessment provides the urologists with only a broad classification, complicated by frequent disagreement among pathologist and the co-existence of different grading systems. Consequently, there is a great need for an objective, reproducible and biologically relevant classification system to make treatment more efficient. In the present investigation we present a molecular taxonomy for UC stratification based on integrated genomics. We used gene expression profiles from 308 UC to define seven molecular subtypes using step-by-step partitions and a bootstrap approach. Results were validated in three independent and publically available data sets. The subtypes differ significantly with respect to expression of cell cycle genes, of receptor tyrosine kinases particularity FGFR3, ERBB2 (HER2), and EGFR, of an FGFR3 associated gene expression signature, of cytokaratins, and of cell adhesion genes. The subtypes also differ significantly with respect to FGFR3, PIK3CA, and TP53 mutations. The expression of key proteins was validated by IHC on TMA. A further inspection indicated that the subtypes could be reduced to four major types of UC; Urobasal/D-driven, Genomically unstable/E-driven, Evolved urobasal, and Basal/SCC like, with characteristic and highly divergent molecular phenotypes. We show that the molecular subtypes cut across pathological classification and that tumors classified as one subtype maintain their characteristic molecular phenotype irrespective of pathological stage and grade. Available data from the Drugbank database and the Cochrane central registry of controlled trials indicate that susceptibility to specific drugs is more likely to be associated with the molecular stratification than with pathological classification. The presented molecular taxonomy stratifies UC into subtypes with distinct molecular phenotypes and biological properties. We anticipate that the molecular taxonomy will be a useful tool in future clinical investigations. Total RNA from fresh-frozen resection samples of 308 urothelial carcinomas was hybridized to the Illumina HumanHT-12 V3.0 expression beadchip arrays (Illumina Inc) at the SCIBLU Genomics Centre at Lund University Sweden (http://www.lth.se/sciblu). Supplementary files: GSE32894_non-normalized_308UCsamples.txt file = Raw intensity values for 308 UC (urothelial tumor) samples subjected only to background correction. GSE32894_reps_normals_preprocess*.txt files = Descriptive details and non-normalized data for technical replicates and normal samples that were used only in the preprocessing of the data. This dataset partly overlaps with Series GSE32549. Names of the overlapping sample names are the same, but the title of each sample is unique to the hybridization.
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