The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer

Umar Wazir, Mai Ahmed, Joanna Bridger 4 , Amanda Harvey 5 , Wen Jiang 6 , Anup Sharma 2 , and Kefah Mokbel
  • 1 London Breast Institute, the Princess Grace Hospital, 45 Nottingham Place, London, W1U 5NY, UK
  • 2 The London Breast Institute, Princess Grace Hospital, London, UK
  • 3 Department of Breast Surgery, St. George’s Hospital and Medical School, University of London, London, UK
  • 4 Centre for Cell & Chromosome Biology, Uxbridge, London, UK
  • 5 Brunel Institute for Cancer Genetics and Pharmacogenomics, School of Health Sciences and Social Care, Brunel University, Uxbridge, London, UK
  • 6 Metastasis and Angiogenesis Research Group, University Department of Surgery, Cardiff University School of Medicine, Cardiff University, Cardiff, Wales, UK

Abstract

Lamin A/C (LMNA), lamin B1 (LMNB1) and lamin B receptor (LBR) have key roles in nuclear structural integrity and chromosomal stability. In this study, we have studied the relationships between the mRNA expressions of A-type lamins, LMNB1 and LBR and the clinicopathological parameters in human breast cancer. Samples of breast cancer tissues (n = 115) and associated non-cancerous tissue (ANCT; n = 30) were assessed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher levels of A-type lamins and LMNB1 mRNA expression were seen in ANCT. Higher lamin A/C expression was associated with the early clinical stage (TNM1 vs. TNM3 — 13 vs. 0.21; p = 0.0515), with better clinical outcomes (disease-free survival vs. mortality — 11 vs. 1; p = 0.0326), and with better overall (p = 0.004) and disease-free survival (p = 0.062). The expression of LMNB1 declined with worsening clinical outcome (disease-free vs. mortalities — 0.0011 vs. 0.000; p = 0.0177). LBR mRNA expression was directly associated with tumor grade (grade 1 vs. grade 3 — 0.00 vs. 0.00; p = 0.0479) and Nottingham Prognostic Index (NPI1 vs. NPI3 — 0.00 vs. 0.00; p = 0.0551). To the best of our knowledge, this is the first study to suggest such a role for A-type lamins, lamin B1 and LBR in human breast cancer, identifying an important area for further research.

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