Diagnostic values of GHSR DNA methylation pattern in breast cancer

Sandeep Kumar Botla, Amin Moghaddas Gholami, Mahdi Malekpour, Evgeny A. Moskalev, Mahdi Fallah, Pouria Jandaghi, Ali Aghajani, Irina S. Bondar, Ramesh Omranipour, Fatemeh Malekpour, Abbas Mohajeri, Azin Jahangiri Babadi, Özgür Sahin, Vladimir V. Bubnov, Hossein Najmabadi, Jörg D. Hoheisel, Yasser Riazalhosseini

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (n = 52, p<2.1 × 10 -4) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (n = 65, p<1.9 × 10-7). The signature is associated with SFRP2 and GHSR genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the GHSR methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.

Original languageEnglish (US)
Pages (from-to)705-713
Number of pages9
JournalBreast Cancer Research and Treatment
Volume135
Issue number3
DOIs
StatePublished - Oct 1 2012
Externally publishedYes

Keywords

  • Breast cancer
  • Diagnosis
  • DNA methylation
  • Epigenetics
  • GHSR

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Botla, S. K., Gholami, A. M., Malekpour, M., Moskalev, E. A., Fallah, M., Jandaghi, P., Aghajani, A., Bondar, I. S., Omranipour, R., Malekpour, F., Mohajeri, A., Babadi, A. J., Sahin, Ö., Bubnov, V. V., Najmabadi, H., Hoheisel, J. D., & Riazalhosseini, Y. (2012). Diagnostic values of GHSR DNA methylation pattern in breast cancer. Breast Cancer Research and Treatment, 135(3), 705-713. https://doi.org/10.1007/s10549-012-2197-z