A fine-needle aspiration-based protein signature discriminates benign from malignant breast lesions

Mol Oncol. 2018 Sep;12(9):1415-1428. doi: 10.1002/1878-0261.12350. Epub 2018 Aug 9.

Abstract

There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and to follow-up personalized cancer therapy. Fine-needle aspiration (FNA) biopsy provides ready access to relevant tissues; however, the minute sample amounts require sensitive multiplex molecular analysis to achieve clinical utility. We have applied proximity extension assays (PEA) and NanoString (NS) technology for analyses of proteins and of RNA, respectively, in FNA samples. Using samples from patients with breast cancer (BC, n = 25) or benign lesions (n = 33), we demonstrate that these FNA-based molecular analyses (a) can offer high sensitivity and reproducibility, (b) may provide correct diagnosis in shorter time and at a lower cost than current practice, (c) correlate with results from routine analysis (i.e., benchmarking against immunohistochemistry tests for ER, PR, HER2, and Ki67), and (d) may also help identify new markers related to immunotherapy. A specific 11-protein signature, including FGF binding protein 1, decorin, and furin, distinguished all cancer patient samples from all benign lesions in our main cohort and in smaller replication cohort. Due to the minimally traumatic sampling and rich molecular information, this combined proteomics and transcriptomic methodology is promising for diagnostics and evaluation of treatment efficacy in BC.

Keywords: breast cancer diagnosis; fine-needle aspiration; protein biomarker; proximity extension assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aftercare
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers, Tumor / analysis*
  • Biopsy, Fine-Needle / economics
  • Breast / pathology
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / therapy
  • Carrier Proteins / analysis
  • Chemokine CXCL9 / analysis
  • Cohort Studies
  • Decorin / analysis
  • Early Diagnosis
  • Female
  • Furin / analysis
  • Heme Oxygenase-1 / analysis
  • Humans
  • Intercellular Signaling Peptides and Proteins / analysis
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Receptor, ErbB-2 / analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CXCL9 protein, human
  • Carrier Proteins
  • Chemokine CXCL9
  • DCN protein, human
  • Decorin
  • GPNMB protein, human
  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • FGFBP1 protein, human
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • FURIN protein, human
  • Furin