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Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
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BQ323636.1, a Novel Splice Variant to NCOR2, as a Predictor for Tamoxifen-Resistant Breast Cancer

Chun Gong1,2, Ellen P S Man1, Ho Tsoi1

  • 1Department of Pathology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|February 9, 2018
PubMed

Insights

A novel splice variant, BQ323636.1, from the NCOR2 gene can predict tamoxifen resistance in estrogen receptor-positive breast cancer patients. Its overexpression is linked to poorer survival and metastasis, highlighting its potential as a predictive biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Adjuvant tamoxifen therapy is crucial for estrogen receptor (ER)-positive breast cancer but faces challenges due to drug resistance.
  • Understanding the mechanisms of tamoxifen resistance and identifying predictive biomarkers are critical for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of BQ323636.1, a novel splice variant of the NCOR2 gene, as a predictor of tamoxifen resistance in ER-positive breast cancer.
  • To evaluate the clinical efficacy of BQ323636.1 as a biomarker for predicting treatment response and patient survival.

Main Methods:

  • Generated a monoclonal antibody specific to BQ323636.1 for in vitro and in vivo studies.
  • Utilized immunohistochemistry on tissue microarrays from two independent cohorts (n=358) of ER-positive breast cancer patients treated with tamoxifen.
  • Employed an orthotopic mouse model to assess tamoxifen resistance and BQ323636.1 function.

Main Results:

  • Overexpression of BQ323636.1 in vitro and in mouse models conferred tamoxifen resistance.
  • BQ323636.1 binds to NCOR2, inhibiting corepressor complex formation and suppressing ER signaling.
  • Nuclear BQ323636.1 overexpression in patient samples significantly correlated with tamoxifen resistance (P = 1.79 × 10⁻⁶), metastasis, and relapse.
  • BQ323636.1 overexpression was associated with poorer overall survival (P = 1.13 × 10⁻⁴) and disease-specific survival (P = 4.02 × 10⁻⁵).

Conclusions:

  • BQ323636.1 serves as a reliable biomarker for predicting tamoxifen resistance in ER-positive breast cancer.
  • The findings support the clinical utility of BQ323636.1 for patient stratification and treatment decisions.

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