Gene signature predicts outcomes in breast cancer

  • Cassetta L & al.
  • Cancer Cell
  • 15 Apr 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Study identified 37-gene tumor-associated macrophages (TAMs) signature which is highly expressed in aggressive breast cancers and associated with worse cancer-specific survival (CSS).
  • An autoregulatory loop between TAMs and cancer cells through colony-stimulating factor (CSF) and tumor necrosis factor α (TNF-α) upregulates potential markers, SIGLEC1 and CCL8.
  • In estrogen-receptor (ER)-positive human epidermal growth factor receptor (HER)-negative patients, high SIGLEC1/CCL8 expression was associated with worse CSS.

Why this matters

  • TAMs and the specific markers they upregulate may be useful for diagnosis or prognosis, or even as therapeutic targets.

Key highlights

  • RNA sequencing was performed in total monocytes from women with breast cancer and healthy women without cancer; significant transcriptional differences were observed in monocytes between healthy women and those with cancer.
  • 37-gene TAM signature highly expressed in the most aggressive breast cancer subtypes were identified.
  • CSF1-high patient group had a significantly higher TAM signature score compared with CSF1-mid and CSF1-low groups, suggesting that TAMs are associated with more aggressive tumors.
  • High TAM expression was associated with shorter CSS.
  • An autoregulatory loop between TAMs and cancer cells through CSF and TNF-α upregulates SIGLEC1 and CCL8.
  • SIGLEC1, a breast cancer TAM-associated marker, was the most highly differentially expressed in TAMs and showed association with poor clinical outcomes.
  • CCL8 is the top upregulated soluble factor associated with breast cancer TAMs.
  • In ER-positive HER-negative patients, high SIGLEC1/CCL8 expression was associated with worse CSS.

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