Cutoff Finder: A Comprehensive and Straightforward Web Application Enabling Rapid Biomarker Cutoff Optimization

TLDR

Gene and protein expression data are continuous or ordinal, yet clinical decisions require a cutoff to dichotomize patients, and no standard method or software exists for this purpose. We created Cutoff Finder, an online suite of optimization and visualization tools for biomarker cutoff determination. The tool offers methods based on marker distribution alone or on optimizing the correlation between dichotomization and an outcome or survival variable. Using breast cancer ER and PgR expression, Cutoff Finder demonstrates how marker distributions can be linked to immunohistological status and distant‑metastasis‑free survival, illustrating its potential to accelerate biomarker development. The application is available at http://molpath.charite.de/cutoff.

Abstract

Gene or protein expression data are usually represented by metric or at least ordinal variables. In order to translate a continuous variable into a clinical decision, it is necessary to determine a cutoff point and to stratify patients into two groups each requiring a different kind of treatment. Currently, there is no standard method or standard software for biomarker cutoff determination. Therefore, we developed Cutoff Finder, a bundle of optimization and visualization methods for cutoff determination that is accessible online. While one of the methods for cutoff optimization is based solely on the distribution of the marker under investigation, other methods optimize the correlation of the dichotomization with respect to an outcome or survival variable. We illustrate the functionality of Cutoff Finder by the analysis of the gene expression of estrogen receptor (ER) and progesterone receptor (PgR) in breast cancer tissues. This distribution of these important markers is analyzed and correlated with immunohistologically determined ER status and distant metastasis free survival. Cutoff Finder is expected to fill a relevant gap in the available biometric software repertoire and will enable faster optimization of new diagnostic biomarkers. The tool can be accessed at http://molpath.charite.de/cutoff.