Gene expression profiling can predict the outcome of stage II colon cancer patients

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.

Download Full-text

Gene Expression Profiling of Nonneoplastic Mucosa May Predict Clinical Outcome of Colon Cancer Patients

Yearbook of Surgery ◽

10.1016/s0090-3671(08)70228-3 ◽

2007 ◽

Vol 2007 ◽

pp. 306-307

Author(s):

T.J. Eberlein

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Clinical Outcome ◽

Gene Expression Profiling ◽

Cancer Patients ◽

Expression Profiling

Download Full-text

Prognosis prediction of stage II colon cancer by gene expression profiling

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.3565 ◽

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.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.613 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 613-613 ◽

Cited By ~ 1

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.

Download Full-text

Gene Expression Profiling of Nonneoplastic Mucosa May Predict Clinical Outcome of Colon Cancer Patients

Diseases of the Colon & Rectum ◽

10.1007/s10350-005-0175-9 ◽

2005 ◽

Vol 48 (12) ◽

pp. 2238-2248 ◽

Cited By ~ 23

Author(s):

Alain Barrier ◽

Pierre-Yves Boelle ◽

Antoinette Lemoine ◽

Chantal Tse ◽

Didier Brault ◽

...

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Clinical Outcome ◽

Gene Expression Profiling ◽

Cancer Patients ◽

Expression Profiling

Download Full-text

Association of chemotherapy with survival in stage II colon cancer patients who received radical surgery: a retrospective cohort study

BMC Cancer ◽

10.1186/s12885-021-08057-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhihao Lv ◽

Yuqi Liang ◽

Huaxi Liu ◽

Delong Mo

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Prediction Models ◽

Radical Surgery ◽

Survival Rates ◽

Stage Ii ◽

Survival Prediction ◽

Stage Ii Colon Cancer ◽

Overall Survival Rates

Abstract Background It remains controversial whether patients with Stage II colon cancer would benefit from chemotherapy after radical surgery. This study aims to assess the real effectiveness of chemotherapy in patients with stage II colon cancer undergoing radical surgery and to construct survival prediction models to predict the survival benefits of chemotherapy. Methods Data for stage II colon cancer patients with radical surgery were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (1:1) was performed according to receive or not receive chemotherapy. Competitive risk regression models were used to assess colon cancer cause-specific death (CSD) and non-colon cancer cause-specific death (NCSD). Survival prediction nomograms were constructed to predict overall survival (OS) and colon cancer cause-specific survival (CSS). The predictive abilities of the constructed models were evaluated by the concordance indexes (C-indexes) and calibration curves. Results A total of 25,110 patients were identified, 21.7% received chemotherapy, and 78.3% were without chemotherapy. A total of 10,916 patients were extracted after propensity score matching. The estimated 3-year overall survival rates of chemotherapy were 0.7% higher than non- chemotherapy. The estimated 5-year and 10-year overall survival rates of non-chemotherapy were 1.3 and 2.1% higher than chemotherapy, respectively. Survival prediction models showed good discrimination (the C-indexes between 0.582 and 0.757) and excellent calibration. Conclusions Chemotherapy improves the short-term (43 months) survival benefit of stage II colon cancer patients who received radical surgery. Survival prediction models can be used to predict OS and CSS of patients receiving chemotherapy as well as OS and CSS of patients not receiving chemotherapy and to make individualized treatment recommendations for stage II colon cancer patients who received radical surgery.

Download Full-text