Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization

PLoS One. 2012;7(12):e51862. doi: 10.1371/journal.pone.0051862. Epub 2012 Dec 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Female
  • Gene Expression
  • Humans
  • Internet*
  • Prognosis
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics*
  • Receptors, Progesterone / biosynthesis
  • Receptors, Progesterone / genetics*
  • Software*

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone

Grants and funding

This work was funded by the European Commission within FP7, grants #200327 (METAcancer) and #257669 (ARROWS), and by OTKA, (Orszagos Tudomanyos Kutatasi Alap Hungarian National Scientific Research Fund) PD 83154. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.