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SRP087576
Homo sapiens
61 Downloadable Samples
Illumina HiSeq 2000
Description
Background: The KRAS gene is mutated in about 40% of colorectal cancer (CRC) cases, which has been clinically validated as a predictive mutational marker of intrinsic resistatnce to anti-EGFR inhibitor (EGFRi) therapy. Since nearly 60% of patients with a wild type KRAS fail to respond to EGFRi treatment, there is a need to develop more reliable molecular signatures to better predict response. Here we address the challenge of adapting a gene expression signature predictive of RAS pathway activation, created using fresh frozen (FF) tissues, for use with more widely available formalin fixed paraffin-embedded (FFPE) tissues. Methods: In this study, we evaluated the translation of an 18-gene RAS pathway signature score from FF to FFPE in 54 CRC cases, using a head-to-head comparison of five technology platforms. FFPE-based technologies included the Affymetrix GeneChip (Affy), NanoString nCounter(NanoS), Illumina whole genome RNASeq (RNA-Acc), Illumina targeted RNASeq(t-RNA), and Illumina stranded Total RNA-rRNA-depletion (rRNA). Results: Using Affy_FF as the "gold" standard, initial analysis of the 18-gene RAS scores on all 54 samples shows varying pairwise Spearman correlations, with (1) Affy_FFPE(r=0.233, p=0.090); (2) NanoS_FFPE(r=0.608, p<0.0001); (3) RNA-Acc_FFPE(r=0.175, p=0.21); (4) t-RNA_FFPE (r=-0.237, p=0.085); and (5) t-RNA (r=-0.012, p=0.93). These results suggest that only NanoString has successful FF to FFPE translation. The subsequent removal of identified "problematic" samples (n=15) and gene (n=2) further improves the correlations of Affy_FF with three of the five technologies: Affy_FFPE (r=0.672, p<0.0001); NanoS_FFPE (r=0.738, p<0.0001); and RNA-Acc_FFPE (r=0.483, p=0.002). Conclusions: Of the five technology platforms tested, NanoString technology provides a more faithful translation of the RAS pathway gene expression signature from FF to FFPE than the Affymetrix GeneChip and multiple RNASeq technologies. Moreover, NanoString was the most forgiving technology in the analysis of samples with presumably poor RNA quality. Using this approach, the RAS signature score may now be reasonably applied to FFPE clinical samples. Overall design: Fifty-four (54) FFPE evaluable tumor specimens were selected from a larger multi-center cohort of 468 well-characterized colorectal adenocarcinoma patients whose tissues were obtained between October 2006 and September 2010 at the University of South Florida. The sample cohort was composed of tumor samples that were available as matched fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) pairs.
Publication Title
Adaptation of a RAS pathway activation signature from FF to FFPE tissues in colorectal cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 65 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Compariosn of mRNA and miRNA profile in colon cancer
Publication Title
Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 185 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of 143 completely histologically-normal breast tissues resulted in the identification of a malignancy risk gene signature that may serve as a marker of subsequent risk of breast cancer development.
Publication Title
Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 153 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Samples were taken from colorectal cancers in surgically resected specimens in 155 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. Our MSI/MSS classifier was applied to these samples.
Publication Title
DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Samples were taken from colorectal cancers in surgically resected specimens from 74 patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. Our MSI/MSS classifer was applied to these samples.
Publication Title
DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Three-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is increasingly appreciated that properties of cultured epithelial cells differ dramatically in 2D compared to 3D, and the latter more faithfully recapitulates in vivo behavior. By studying a battery of human colorectal cancer (CRC) cell lines in type-1 collagen, we have found that HCA-7 cells form colonies with two distinctive and persistent morphological and functional properties. We observed predominantly single-layered polarized cysts (cystic colonies, CC) and a smaller fraction displaying disorganized solid masses (spiky colonies, SC) that were highly invasive in vivo. Despite overall genomic similarity, CC and SC exhibited distinct and dynamic patterns of gene expression in 3D.
Publication Title
Three-dimensional culture system identifies a new mode of cetuximab resistance and disease-relevant genes in colorectal cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 289 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Samples were taken from colorectal cancers in surgically resected specimens in 290 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133Plus 2.0 arrays. The training set of our prognosis classifier included the stage A and D samples. Validation used our stage B and C samples.
Publication Title
Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 234 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sample Metadata Fields
Sex, Age, Disease stage, Race
View Samples