NT5E CpG island methylation is a favourable breast cancer biomarker

C. Lo Nigro, M. Monteverde, S. Lee, L. Lattanzio, D. Vivenza, A. Comino, N. Syed, A. McHugh, H. Wang, C. Proby, O. Garrone, M. Merlano, E. Hatzimichael, E. Briasoulis, O. Gojis, C. Palmieri, L. Jordan, P. Quinlan, A. Thompson, T. Crook

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    Abstract

    Background: Relapse risk assessment and individual treatment recommendations remain suboptimal for breast cancer patients. In the light of existing preclinical and clinical data, we studied NT5E (5'-nucleotidase, ecto) expression and NT5E CpG island methylation in breast cancer. Methods: We used RT-PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse NT5E in breast carcinoma cell lines and primary and breast carcinomas. Results: NT5E CpG island methylation was inversely associated with NT5E expression in breast carcinoma cell lines. In clinical series, patients whose primary tumours had NT5E CpG island methylation were less likely to develop metastasis (P=0.003, OR=0.34, 95% CI: 0.17-0.69). In 3/4 paired samples, NT5E was methylated in primary tumours and demethylated in CNS metastases. Patients progressing to non-visceral as compared with visceral metastases were more likely to have NT5E CpG island methylation in primary tumours (P=0.01, OR=11.8). Patients with tumours lacking detectable methylation had shorter disease-free survival (DFS) (P=0.001, HR=2.7) and overall survival (OS) (P=0.001, HR=3). The favourable prognostic value of NT5E methylation was confirmed in oestrogen receptor negative (P=0.011, HR=3.27, 95% CI: 1.31-8.12) and in triple negative cases (P=0.004; HR=6.2, 95% CI: 1.9-20). Moreover, we observed a more favourable outcome to adjuvant chemotherapy in patients whose tumours were positive for NT5E CpG island methylation: DFS (P=0.0016, HR=5.1, 95% CI: 1.8-14.37) and OS (P=0.0005, HR=7.4, 95% CI: 2.416-23.08). Conclusion: NT5E CpG island methylation is a promising breast cancer biomarker.
    Original languageEnglish
    Pages (from-to)75-83
    Number of pages9
    JournalBritish Journal of Cancer
    Volume107
    Issue number1
    DOIs
    Publication statusPublished - 2012

    Fingerprint Dive into the research topics of 'NT5E CpG island methylation is a favourable breast cancer biomarker'. Together they form a unique fingerprint.

  • Cite this

    Lo Nigro, C., Monteverde, M., Lee, S., Lattanzio, L., Vivenza, D., Comino, A., Syed, N., McHugh, A., Wang, H., Proby, C., Garrone, O., Merlano, M., Hatzimichael, E., Briasoulis, E., Gojis, O., Palmieri, C., Jordan, L., Quinlan, P., Thompson, A., & Crook, T. (2012). NT5E CpG island methylation is a favourable breast cancer biomarker. British Journal of Cancer, 107(1), 75-83. https://doi.org/10.1038/bjc.2012.212