Merging microarray data from separate breast cancer studies provides a robust prognostic test Export

@article{citeulike:2446244, abstract = {BACKGROUND:There is an urgent need for new prognostic markers of breast cancer metastases to ensure that newly diagnosed patients receive appropriate therapy. Recent studies have demonstrated the potential value of gene expression signatures in assessing the risk of developing distant metastases. However, due to the small sample sizes of individual studies, the overlap among signatures is almost zero and their predictive power is often limited. Integrating microarray data from multiple studies in order to increase sample size is therefore a promising approach to the development of more robust prognostic tests.RESULTS:In this study, by using a highly stable data aggregation procedure based on expression comparisons, we have integrated three independent microarray gene expression data sets for breast cancer and identified a structured prognostic signature consisting of 112 genes organized into 80 pair-wise expression comparisons. A classical likelihood ratio test based on these comparisons, essentially weighted voting, achieves 88.6\% sensitivity and 54.6\% specificity in an independent external test set of 154 samples. The test is highly informative in assessing the risk of developing distant metastases within five years (hazard ratio 9.3 with 95\% CI 2.9-29.9).CONCLUSION:Rank-based features provide a stable way to integrate patient data from separate microarray studies due to invariance to data normalization, and such features can be combined into a useful predictor of distant metastases in breast cancer within a statistical modeling framework which begins to capture gene-gene interactions. Upon further confirmation on large-scale independent data, such prognostic signatures and tests could provide a powerful tool to guide adjuvant systemic treatment that could greatly reduce the cost of breast cancer treatment, both in terms of toxic side effects and health care expenditures.}, author = {Xu, Lei and Tan, Aik and Winslow, Raimond and Geman, Donald}, citeulike-article-id = {2446244}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2105-9-125}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18304324}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18304324}, day = {27}, doi = {10.1186/1471-2105-9-125}, issn = {1471-2105}, journal = {BMC Bioinformatics}, keywords = {breast, cancer, expression, genesignature}, month = {February}, number = {1}, pages = {125+}, posted-at = {2008-06-26 21:24:27}, priority = {3}, title = {Merging microarray data from separate breast cancer studies provides a robust prognostic test}, url = {http://dx.doi.org/10.1186/1471-2105-9-125}, volume = {9}, year = {2008} }

TY - JOUR ID - citeulike:2446244 L3 - citeulike-article-id:2446244 N2 - BACKGROUND:There is an urgent need for new prognostic markers of breast cancer metastases to ensure that newly diagnosed patients receive appropriate therapy. Recent studies have demonstrated the potential value of gene expression signatures in assessing the risk of developing distant metastases. However, due to the small sample sizes of individual studies, the overlap among signatures is almost zero and their predictive power is often limited. Integrating microarray data from multiple studies in order to increase sample size is therefore a promising approach to the development of more robust prognostic tests.RESULTS:In this study, by using a highly stable data aggregation procedure based on expression comparisons, we have integrated three independent microarray gene expression data sets for breast cancer and identified a structured prognostic signature consisting of 112 genes organized into 80 pair-wise expression comparisons. A classical likelihood ratio test based on these comparisons, essentially weighted voting, achieves 88.6% sensitivity and 54.6% specificity in an independent external test set of 154 samples. The test is highly informative in assessing the risk of developing distant metastases within five years (hazard ratio 9.3 with 95% CI 2.9-29.9).CONCLUSION:Rank-based features provide a stable way to integrate patient data from separate microarray studies due to invariance to data normalization, and such features can be combined into a useful predictor of distant metastases in breast cancer within a statistical modeling framework which begins to capture gene-gene interactions. Upon further confirmation on large-scale independent data, such prognostic signatures and tests could provide a powerful tool to guide adjuvant systemic treatment that could greatly reduce the cost of breast cancer treatment, both in terms of toxic side effects and health care expenditures. IS - 1 JF - BMC Bioinformatics SN - 1471-2105 TI - Merging microarray data from separate breast cancer studies provides a robust prognostic test VL - 9 SP - 125 KW - breast KW - cancer KW - expression KW - genesignature AU - Xu, Lei AU - Tan, Aik AU - Winslow, Raimond AU - Geman, Donald PY - 2008/02/27/ UR - http://dx.doi.org/10.1186/1471-2105-9-125 ER -