Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes

Nat Commun. 2018 Mar 23;9(1):1219. doi: 10.1038/s41467-018-03631-z.


Assessing the phenotypic diversity underlying tumour progression requires the identification of variations in the respective molecular interaction networks. Here we report proof-of-concept for a platform called poly-ligand profiling (PLP) that surveys these system states and distinguishes breast cancer patients who did or did not derive benefit from trastuzumab. We perform tissue-SELEX on breast cancer specimens to enrich single-stranded DNA (ssDNA) libraries that preferentially interact with molecular components associated with the two clinical phenotypes. Testing of independent sample sets verifies the ability of PLP to classify trastuzumab-treated patients according to their clinical outcomes with ROC-AUC of 0.78. Standard HER2 testing of the same patients gives a ROC-AUC of 0.47. Kaplan-Meier analysis reveals a median increase in benefit from trastuzumab-containing treatments of 300 days for PLP-positive compared to PLP-negative patients. If prospectively validated, PLP may increase success rates in precision oncology and clinical trials, thus improving both patient care and drug development.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Area Under Curve
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • DNA, Single-Stranded / analysis
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Ligands
  • Middle Aged
  • Phenotype
  • Precision Medicine
  • SELEX Aptamer Technique
  • Sequence Analysis, DNA
  • Trastuzumab / therapeutic use*
  • Treatment Outcome


  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • DNA, Single-Stranded
  • Ligands
  • Trastuzumab