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Development and Independent Validation of a Prognostic Assay for Stage II Colon Cancer using Formalin Fixed Paraffin Embedded Tissue_Validation Set

ABSTRACT: Current prognostic factors are poor at identifying patients at risk of disease recurrence following surgery for stage II colon cancer. Here we describe a DNA microarray based prognostic assay using clinically relevant formalin fixed paraffin embedded (FFPE) samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Peter Hey

PROVIDER: E-MTAB-864 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue.

Kennedy Richard D RD Bylesjo Max M Kerr Peter P Davison Timothy T Black Julie M JM Kay Elaine W EW Holt Robert J RJ Proutski Vitali V Ahdesmaki Miika M Farztdinov Vadim V Goffard Nicolas N Hey Peter P McDyer Fionnuala F Mulligan Karl K Mussen Julie J O'Brien Eamonn E Oliver Gavin G Walker Steven M SM Mulligan Jude M JM Wilson Claire C Winter Andreas A O'Donoghue Diarmuid D Mulcahy Hugh H O'Sullivan Jacintha J Sheahan Kieran K Hyland John J Dhir Rajiv R Bathe Oliver F OF Winqvist Ola O Manne Upender U Shanmugam Chandrakumar C Ramaswamy Sridhar S Leon Eduardo J EJ Smith William I WI McDermott Ultan U Wilson Richard H RH Longley Daniel D Marshall John J Cummins Robert R Sargent Daniel J DJ Johnston Patrick G PG Harkin D Paul DP

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20111107 35

<h4>Purpose</h4>Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.<h4>Patients and methods</h4>A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery.<h4>Results</h4>The ...[more]

PMID: 22067406

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Project description:Purpose: Despite advances in radical surgery and chemotherapy delivery, ovarian cancer is the most lethal gynecologic malignancy. Most of these patients are treated with platinum-based chemotherapies, but there is no biomarker model to guide their responses to these therapeutic agents. We have developed and independently tested our novel multivariate molecular predictors for forecasting patients' responses to individual drugs on a cohort of 58 ovarian cancer patients. Experimental Design: We adapted and applied the previously-published COXEN algorithm to develop molecular predictors for therapeutic responses of patients' tumors based on expression signatures derived from the NCI-60 in vitro drug activities and genomic expression data. Genome-wide candidate biomarkers were first triaged by examining expression patterns of frozen and formalin-fixed paraffin embedded (FFPE) tissue samples. We then identify initial drug sensitivity biomarkers for carboplatin and paclitaxel, respectively. These biomarkers were further narrowed by examining concordant expression patterns between cell lines and a historical set of ovarian cancer patients. Multivariate predictors were obtained from the NCI-60 cell lines and refined using historical patient cohorts. To independent validate these molecular predictors, we performed genome-wide profiling on FFPE samples of 58 ovarian cancer patients obtained prior to adjuvant chemotherapy. Results: Carboplatin predictor significantly stratified platinum sensitive and resistant patients (p = 0.019) with sensitivity = 93%, specificity = 33%, PPV = 65%, and NPV = 78%. Paclitaxel predictor also significantly stratified patients' responses (p = 0.033) with sensitivity = 96%, specificity = 26%, PPV = 61%, and NPV = 86%. The combination predictor for platinum-taxane combination demonstrated a significant survival difference between the predicted responders and nonresponders with median survival of 12.9 months vs. 8.1 months (p = 0.045). Conclusions: COXEN predictors successfully stratified platinum resistance and taxane response in this retrospective cohort, especially based on their FFPE tumor samples. Accurate prediction of chemotherapeutic response, especially to platinum agents is highly clinically relevant and could alter primary management of ovarian cancer. Gene expression data from 58 stage III-IV ovarian cancer patients treated with Carboplatin and Taxol agents

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Dataset Information

Development and Independent Validation of a Prognostic Assay for Stage II Colon Cancer using Formalin Fixed Paraffin Embedded Tissue_Validation Set

Publications

Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue.

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