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Predicting features of breast cancer with gene expression patterns

  • Xuesong Lu
  • Xin Lu
  • Zhigang C. Wang
  • J. Dirk Iglehart
  • Xuegong ZhangEmail author
  • Andrea L. RichardsonEmail author
Preclinical Study

Abstract

Data from gene expression arrays hold an enormous amount of biological information. We sought to determine if global gene expression in primary breast cancers contained information about biologic, histologic, and anatomic features of the disease in individual patients. Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers [estrogen receptor (ER) and HER2], histologic features [grade and lymphatic-vascular invasion (LVI)], and stage parameters (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy was determined by cross-validation error rate; multidimensional scaling (MDS) allowed visualization of the predicted states under study. Models built from gene expression data accurately predict ER and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data is inaccurate at predicting tumor size, lymph node status or LVI. The best model for prediction of nodal status included tumor size, LVI status and pathologically defined tumor subtype (based on combinations of ER, HER2, and grade); the addition of microarray-based prediction to this model failed to improve the prediction accuracy. Global gene expression supports a binary division of ER, HER2, and grade, clearly separating tumors into two categories; intermediate values for these bio-indicators do not define intermediate tumor subsets. Results are consistent with a model of regional metastasis that depends on inherent biologic differences in metastatic propensity between breast cancer subtypes, upon which time and chance then operate.

Keywords

Breast cancer Computational molecular biology Gene expression profiling Metastasis 

Notes

Acknowledgements

Supported by the Breast Cancer Research Foundation (BCRF) and by the Dana-Faber/Harvard SPORE in Breast Cancer from the National Cancer Institute (J.D.I., A.R.), grants ACS-IRG 70-002 and CA23100-22 (X.L), NSFC grant 30625012 and the National Basic Research Program (2004CB518605) of China (X.Z.).

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Xuesong Lu
    • 1
  • Xin Lu
    • 2
    • 3
    • 4
  • Zhigang C. Wang
    • 5
    • 6
  • J. Dirk Iglehart
    • 5
    • 6
  • Xuegong Zhang
    • 1
    Email author
  • Andrea L. Richardson
    • 7
    Email author
  1. 1.Bioinformatics Division, TNLIST and Department of AutomationTsinghua UniversityBeijingChina
  2. 2.Department of BiostatisticsHarvard School of Public HealthBostonUSA
  3. 3.Department of BiostatisticsDana-Farber Cancer InstituteBostonUSA
  4. 4.Department of Family and Preventive MedicineUniversity of California San DiegoSan DiegoUSA
  5. 5.Department of SurgeryBrigham and Women’s HospitalBostonUSA
  6. 6.Department of Cancer BiologyDana-Farber Cancer InstituteBostonUSA
  7. 7.Department of PathologyBrigham and Women’s HospitalBostonUSA

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