CITED1 as a marker of favourable outcome in anti-endocrine treated, estrogen-receptor positive, lymph-node negative breast cancer.

Malin Dahlgren, Barbara Lettiero, Hina Dalal, Kira Mårtensson, Alexander Gaber, Björn Nodin, Sofia Gruvberger, Lao H Saal, Jillian Howlin

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To investigate CITED1 as a potential biomarker of anti-endocrine response and breast cancer recurrence, given its previously determined role in mediating estrogen-dependant transcription. The study is a continuation of earlier work establishing the role of CITED1 in mammary gland development.

Results: CITED1 mRNA is associated with estrogen-receptor positivity and selectively expressed in the GOBO dataset of cell lines and tumours representing the luminal-molecular subtype. In patients treated with tamoxifen, higher CITED1 correlated with better outcome, suggesting a role in anti-estrogen response. The effect was particularly evident in the subset of estrogen-receptor positive, lymph-node negative (ER+/LN-) patients although noticeable divergence of the groups was apparent only after five years. Tissue microarray (TMA) analysis further validated the association of CITED1 protein, by immunohistochemistry, with favourable outcome in ER+, tamoxifen-treated patients. Although we also found a favourable response to anti-endocrine treatment in a larger TCGA dataset, the tamoxifen-specific effect was not replicated. Finally, MCF7 cells overexpressing CITED1 showed selective amplification of AREG but not TGFα suggesting that maintenance of specific ERα-CITED1 mediated transcription is important for the long-term response to anti-endocrine therapy. These findings together confirm the proposed mechanism of action of CITED1 and support its potential use as a prognostic biomarker.
Original languageEnglish
Article number105
JournalBMC Research Notes
Volume16
Issue number1
DOIs
Publication statusPublished - 2023 Jun 15

Subject classification (UKÄ)

  • Cancer and Oncology

Free keywords

  • breast cancer
  • ER alpha
  • CITED1
  • tamoxifen
  • aromatase inhibitor
  • Anti-endocrine

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