Title | Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Stopsack KH, Tyekucheva S, Wang M, Gerke TA, J Vaselkiv B, Penney KL, Kantoff PW, Finn SP, Fiorentino M, Loda M, Lotan TL, Parmigiani G, Mucci LA |
Journal | Elife |
Volume | 10 |
Date Published | 2021 Dec 23 |
ISSN | 2050-084X |
Keywords | Biomarkers, Tumor, Humans, Male, Prostatic Neoplasms, Tissue Array Analysis |
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 1448 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. |
DOI | 10.7554/eLife.71265 |
Alternate Journal | Elife |
PubMed ID | 34939926 |
PubMed Central ID | PMC8849344 |
Grant List | P50 CA090381 / CA / NCI NIH HHS / United States R37 CA227190 / CA / NCI NIH HHS / United States U01 CA167552 / CA / NCI NIH HHS / United States R35 CA212799 / CA / NCI NIH HHS / United States P30 CA006516 / CA / NCI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 CA131945 / CA / NCI NIH HHS / United States R03 CA212799 / CA / NCI NIH HHS / United States P50 CA211024 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.