17 research outputs found
Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays
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
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A prospective study of aspirin use and prostate cancer risk by TMPRSS2:ERG status
Background: In a case-control study, aspirin use was associated with a lower risk of a common prostate cancer molecular subtype, the TMPRSS2:ERG gene fusion. We sought to validate this finding in a prospective cohort.Methods: In the Health Professionals Follow-up Study, 49,395 men reported on aspirin use on biennial questionnaires and were followed for prostate cancer incidence over 23 years. TMPRSS2:ERG status was assessed by IHC for presence of ERG on archival tumor specimens for 912 patients with prostate cancer, of whom 48% were ERG-positive.Results: In multivariable models, we found no association between regular use of aspirin and risk of ERG-positive prostate cancer (HR, 1.02; 95% confidence interval, 0.85-1.23), nor any association with duration or frequency of aspirin use. In restricting to cases with either high Gleason grade or advanced stage disease, there remained no association with aspirin use.Conclusions: Data from this prospective study with repeated assessments of aspirin use do not support the hypothesis that aspirin use is associated with a lower risk of ERG-positive prostate cancer.Impact: Aspirin use is unlikely to lower the risk of this common molecular subtype of prostate cancer. However, there is emerging data supporting the role of other lifestyle and genetic factors underlying the development of the TMPRSS2:ERG fusion. Cancer Epidemiol Biomarkers Prev; 27(10); 1231-3. ©2018 AACR