Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays Journal Article
| Authors: | Stopsack, K. H.; Tyekucheva, S.; Wang, M.; Gerke, T. A.; Vaselkiv, B.; Penney, K. L.; Kantoff, P. W.; Finn, S. P.; Fiorentino, M.; Loda, M.; Lotan, T. L.; Parmigiani, G.; Mucci, L. A. |
| Article 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. © 2021, eLife Sciences Publications Ltd. All rights reserved. |
| Keywords: | immunohistochemistry; controlled study; human tissue; cancer staging; prospective study; biological marker; gene expression; randomized controlled trial; immunofluorescence; tumor marker; dna methylation; risk factor; mathematical model; prostate cancer; gleason score; simulation; health practitioner; acetylsalicylic acid; molecular epidemiology; hazard ratio; cancer tissue; tissue microarray; estrogen receptor; transurethral resection; urogenital tract disease; vitamin d receptor; measurement error; adipose tissue; estrogen receptor alpha; estrogen receptor beta; human; male; article; tunel assay; batch effects; batchtma r package; batch process |
| Journal Title: | eLife |
| Volume: | 10 |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications Ltd. |
| Date Published: | 2021-12-23 |
| Start Page: | e71265 |
| Language: | English |
| DOI: | 10.7554/eLife.71265 |
| PROVIDER: | scopus |
| PUBMED: | 34939926 |
| PMCID: | PMC8849344 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2022 -- Source: Scopus |
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