@article{70093edc8ef247ee822fc67226c0e245,
title = "Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays",
abstract = "Tissue microarrays (TMAs) have been used in thousands of cancer biomarker studies. To what extent batch effects, measurement error in biomarker levels between slides, affects TMA-based studies has not been assessed systematically. We evaluated 20 protein biomarkers on 14 TMAs with prospectively collected tumor tissue from 1,448 primary prostate cancers. In half of the biomarkers, more than 10% of biomarker variance was attributable to between-TMA differences (range, 1–48%). We implemented different methods to mitigate batch effects (R package batchtma), tested in plasmode simulation. Biomarker levels were more similar between mitigation approaches compared to uncorrected values. For some biomarkers, associations with clinical features changed substantially after addressing batch effects. Batch effects and resulting bias are not an error of an individual study but an inherent feature of TMA-based protein biomarker studies. They always need to be considered during study design and addressed analytically in studies using more than one TMA.",
keywords = "Batch effects, Batchtma R package, Measurement error, Tissue microarray",
author = "Stopsack, {Konrad H.} and Svitlana Tyekucheva and Molin Wang and Gerke, {Travis A.} and Bailey Vaselkiv and Penney, {Kathryn L.} and Kantoff, {Philip W.} and Finn, {Stephen P.} and Michelangelo Fiorentino and Massimo Loda and Lotan, {Tamara L.} and Giovanni Parmigiani and Mucci, {Lorelei A.}",
note = "Funding Information: Research Excellence program in Prostate Cancer P50 CA090381 and P50 CA211024, the NIH/NCI Cancer Center Support Grants P30 CA008748 and P30 CA006516, NIH/NCI grants 5R37 CA227190-02 (S. Tyekucheva, K.L. Penney, G. Parmigiani, and L.A. Mucci), R03 CA212799 (M.W.), R35 CA212799 (M.W.), and R01 CA131945 (M. Loda). The Department of Defense supported K.H. Stopsack (W81XWH-18-1-0330). K.H. Stopsack, K.L. Penney, S.P. Finn, T.L. Lotan, and L.A. Mucci are Prostate Cancer Foundation Young Investigators. Funding Information: We thank the participants and staff of the HPFS and the PHS for their valuable contributions. In particular, we would like to recognize the contributions of Liza Gazeeva, Siobhan Saint-Surin, Robert Sheahan, Betsy Frost-Hawes, and Eleni Konstantis. We would like to thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data. The HPFS is supported by the NIH (U01 CA167552). This research was funded in part by the Specialized Programs of Publisher Copyright: {\textcopyright} 2021, eLife Sciences Publications Ltd. All rights reserved.",
year = "2021",
month = dec,
doi = "10.7554/eLife.71265",
language = "English (US)",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}