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Tumour sampling method can significantly influence gene expression profiles derived from neoadjuvant window studies.

Dominic A Pearce1, Laura M Arthur1, Arran K Turnbull1

  • 1Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Scientific Reports
|July 8, 2016
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Summary

Tumour sampling method significantly impacts gene expression in breast cancer patients, independent of treatment. This finding highlights sampling as a crucial factor to consider in study design.

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Patient-matched transcriptomic studies control for inter-patient heterogeneity but often lack untreated comparisons.
  • Understanding gene expression changes in breast cancer without treatment is crucial for accurate molecular profiling.

Purpose of the Study:

  • To investigate dynamic gene expression changes in breast cancer biopsies before and after surgery in untreated patients.
  • To determine the impact of tumour sampling method and heterogeneity on gene expression profiles.

Main Methods:

  • Illumina BeadArray technology was employed to analyze gene expression.
  • Thirty-seven paired diagnostic core and surgically excised breast cancer biopsies from untreated women were studied.

Main Results:

  • Consistent gene expression changes were observed between diagnosis and surgery, irrespective of subtype or time interval.
  • Tumour sampling method, not treatment or biopsy response, was identified as a primary driver of these gene expression changes.
  • A hypoxic response was implicated following surgical biopsy, rather than wounding or immune responses.

Conclusions:

  • Tumour sampling method is a significant confounding factor in breast cancer research, particularly for neoadjuvant study design.
  • Gene expression changes due to sampling can be secondary to treatment effects in treated samples.
  • Further research should account for sampling-related gene expression alterations.