The expression profile of phosphatidylinositol in high spatial resolution imaging mass spectrometry as a potential biomarker for prostate cancer

PLoS One. 2014 Feb 28;9(2):e90242. doi: 10.1371/journal.pone.0090242. eCollection 2014.

Abstract

High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS) is an emerging application for the comprehensive and detailed analysis of the spatial distribution of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500-1000 was performed on optimal cutting temperature (OCT) compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS) showed that these molecules included 14 phosphatidylinositols (PIs), 3 phosphatidylethanolamines (PEs) and 3 phosphatidic acids (PAs). Among the PIs, the expression of PI(18:0/18:1), PI(18:0/20:3) and PI(18:0/20:2) were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA). The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Algorithms
  • Biomarkers, Tumor / isolation & purification*
  • Biomarkers, Tumor / metabolism
  • Humans
  • Male
  • Middle Aged
  • Phosphatidic Acids / isolation & purification*
  • Phosphatidic Acids / metabolism
  • Phosphatidylethanolamines / isolation & purification*
  • Phosphatidylethanolamines / metabolism
  • Phosphatidylinositols / isolation & purification*
  • Phosphatidylinositols / metabolism
  • Prostatectomy
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / metabolism
  • Sensitivity and Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods

Substances

  • Biomarkers, Tumor
  • Phosphatidic Acids
  • Phosphatidylethanolamines
  • Phosphatidylinositols

Grants and funding

This work was supported by a grant from the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),” initiated by the Council for Science and Technology Policy (CSTP) (http://www.first-ms3d.jp/english/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.