Prognosis prediction of stage II colon cancer by gene expression profiling

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3565-3565
Author(s):  
A. Barrier ◽  
D. Brault ◽  
S. Houry ◽  
S. Dudoit ◽  
A. Lemoine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Expression Profiling ◽  
Prediction Accuracy ◽  
Stage Ii ◽  
Microarray Gene Expression ◽  
Prognosis Prediction ◽  
Learning Set ◽  
Stage Ii Colon Cancer ◽  
High Instability

3565 Background: The aims of the present study were: 1) to identify a prognosis signature (PS), based on microarray gene expression measures, in stage II colon cancer patients and to assess its accuracy with resampling techniques ; 2) to assess the accuracy, also with resampling techniques, of a previously proposed 23-gene PS. Methods: Colon tumor mRNA samples from 50 patients were profiled using the Affymetrix HGU133A GeneChip (22283 sequences). In a first part, the 50 patients were randomly divided into 2 groups (G1 and G2) of equal size that were considered alternately as training and validation sets. In a second part, the 50 patients were randomly divided into 1600 training (size=n) and validation (size=50-n) sets. Informative genes were selected on the training set by taking the 30 most differentially expressed genes between patients who recurred and those who remained disease-free; the accuracy of this PS was assessed by comparing the predicted prognosis (using a diagonal linear discriminant analysis (DLDA)) and the actual evolution for all the validation set patients. Using the same random splits, the accuracy of the 23-gene PS was assessed with a DLDA that used learning set patients as reference samples. Results: The 30-gene PS that was identified from G1 (G2) patients yielded a 80% (84%) prognosis prediction accuracy when applied on G2 (G1) patients. With resampling techniques, the prediction accuracy regularly increased with the learning set (LS) size: 65.5% (range=52.5–75%) with LS of size 10, and 82.7% (range=60–100%) with LS of size 40. Comparisons of compositions of the 100 PS for a given value of n suggested a high instability of informative genes; with LS of size 10, 7 genes were part of at least 10% of signatures; with LS of size 40, 7 genes were part of all the 100 signatures. The accuracy of the previously proposed 23-gene PS also increased with the learning set size. Conclusion: Microarray gene expression profiling represents a promising technique to predict the prognosis of stage II colon cancer patients. The present study also outlines the high instability of informative gene selection and suggests the usefulness of resampling techniques to obtain an honest assessment of prognosis prediction accuracy. No significant financial relationships to disclose.

Stage II Colon Cancer Prognosis Prediction by Tumor Gene Expression Profiling

2006 ◽  
Vol 24 (29) ◽  
pp. 4685-4691 ◽  
Author(s):  
Alain Barrier ◽  
Pierre-Yves Boelle ◽  
François Roser ◽  
Jennifer Gregg ◽  
Chantal Tse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Prediction Accuracy ◽  
Stage Ii ◽  
Prognosis Prediction ◽  
Group 2 ◽  
Stage Ii Colon Cancer ◽  
Group 1

Purpose This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated. Patients and Methods Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes. Results The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy. Conclusion Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.

scholarly journals Prognosis of stage II colon cancer by non-neoplastic mucosa gene expression profiling

Oncogene ◽  
2006 ◽  
Vol 26 (18) ◽  
pp. 2642-2648 ◽  
Author(s):  
A Barrier ◽  
F Roser ◽  
P-Y Boëlle ◽  
B Franc ◽  
C Tse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Stage Ii ◽  
Stage Ii Colon Cancer

scholarly journals A comparison of 12-gene colon cancer assay gene expression in African American and Caucasian patients with stage II colon cancer

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Rangaswamy Govindarajan ◽  
James Posey ◽  
Calvin Y. Chao ◽  
Ruixiao Lu ◽  
Trafina Jadhav ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
African American ◽  
Stage Ii ◽  
Caucasian Patients ◽  
Stage Ii Colon Cancer

Recurrence score distributions in stage II colon cancers of African American (AA) and Caucasian (CA) patients.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 613-613 ◽  
Author(s):  
Rangaswamy Govindarajan ◽  
James Posey ◽  
Calvin Y. Chao ◽  
Ruixiao Lu ◽  
Trafina Jadhav ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Medical Center ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Recurrence Score ◽  
Stage Ii ◽  
Racial Groups ◽  
Stage Ii Colon Cancer

613 Background: The 12-gene colon cancer assay (Oncotype DX) can identify groups of stage II colon cancer patients with lower or higher recurrence risk, but distribution of scores based on race/ethnicity has not been assessed. This study compared the distribution of Recurrence Score results and gene expression profiles between African American (AA) and Caucasian (CA) stage II colon cancer patients. Methods: Stage II colon cancer patients were identified from tumor registry data from four institutions: University of Arkansas for Medical Sciences, Little Rock; Veterans Administration Medical Center, Little Rock; Baptist Medical Center, Memphis, and University of Alabama at Birmingham. The 12-gene assay and mismatch repair (MMR) status were performed on formalin-fixed paraffin-embedded tissues by Genomic Health (Redwood City, CA). T-test and Wilcoxon test were used to compare data from the two groups (SAS Enterprise Guide 5.1). Results: Of the 244 subjects, there were 118 women (63 AA, 55 CA) and 126 men (59 AA, 67 CA). Median ages (years) were 66 for AAs and 68 for CAs. Age, gender, surgery year, pathologic T-Stage, tumor location, number of nodes examined, lympho-vascular invasion, and MMR status were not significantly different between groups (p>0.05). Recurrence Score results between AAs (mean 27.9; SD 12.8) and CAs (mean 28.1; SD 11.8) were not statistically different (p>0.05). The proportion of patients with high Recurrence Score values (≥41) was similar between the groups (17/122 AA; 15/122 CA). None of the gene expression variables, either single genes or gene groups, (cell cycle group, stromal group, BGN1, FAP, INHBA1, Ki67, MYBL2, cMYC3 and GADD45B) was significantly different between the racial groups (p>0.05). After controlling for clinical and pathologic covariates, means and distributions of Recurrence Score and gene expression profiles still showed no statistical significance between racial groups (p>0.05). Conclusions: In a cohort of AA and CA stage II colon cancer patients with similar clinical characteristics, the distribution of Recurrence Score results and gene expression data were similar between AA and CA patients.

Validation Study of a Quantitative Multigene Reverse Transcriptase–Polymerase Chain Reaction Assay for Assessment of Recurrence Risk in Patients With Stage II Colon Cancer

2011 ◽  
Vol 29 (35) ◽  
pp. 4611-4619 ◽  
Author(s):  
Richard G. Gray ◽  
Philip Quirke ◽  
Kelly Handley ◽  
Margarita Lopatin ◽  
Laura Magill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Cox Proportional Hazards ◽  
Stage Ii ◽  
Treatment Benefit ◽  
Risk Of Recurrence ◽  
T Stage ◽  
Stage Ii Colon Cancer

Purpose We developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer. Patients and Methods We sought validation by using RNA extracted from fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer-related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy. Results Risk of recurrence was significantly associated with RS (hazard ratio [HR] per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95). Conclusion The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.

scholarly journals Interconnectivity between molecular subtypes and tumor stage in colorectal cancer

2020 ◽  
Author(s):  
R.R.J. Coebergh van den Braak ◽  
Sanne ten Hoorn ◽  
A.M. Sieuwerts ◽  
J.B. Tuynman ◽  
M. Smid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Molecular Subtypes ◽  
Tnm Classification ◽  
Tumor Biology ◽  
Tumor Stage ◽  
Stage Ii ◽  
Colon Cancers ◽  
Advanced Stages ◽  
Stage Ii Colon Cancer

Abstract Background There are profound individual differences in clinical outcome between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer. Methods We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers. Results CMS4 was significantly more prevalent in advanced stages of disease (III-IV). The observed differential gene expression between cancer stages is predominantly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated. CMS4 cancers showed an increased progression rate to more advanced stages. Indeed, determining CMSs was a relevant addition to TNM classification in identifying stage II colon cancer patients with high-risk of disease recurrence. Conclusions Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, also reflects distinct biological disease entities. These insights can be utilized to optimize identification of high-risk stage II colon cancers.

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