NT5E CpG island methylation is a favourable breast cancer biomarker
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Author(s)
Type
Journal Article
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 (50
-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 ¼ 0.003, OR ¼ 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 ¼ 0.01, OR ¼ 11.8). Patients with tumours lacking detectable methylation had shorter disease-free survival (DFS)
(P ¼ 0.001, HR ¼ 2.7) and overall survival (OS) (P ¼ 0.001, HR ¼ 3). The favourable prognostic value of NT5E methylation was
confirmed in oestrogen receptor negative (P ¼ 0.011, HR ¼ 3.27, 95% CI: 1.31–8.12) and in triple negative cases (P ¼ 0.004;
HR ¼ 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 ¼ 0.0016, HR ¼ 5.1, 95% CI: 1.8–14.37) and OS (P ¼ 0.0005,
HR ¼ 7.4, 95% CI: 2.416–23.08).
CONCLUSION: NT5E CpG island methylation is a promising breast cancer biomarker
light of existing preclinical and clinical data, we studied NT5E (50
-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 ¼ 0.003, OR ¼ 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 ¼ 0.01, OR ¼ 11.8). Patients with tumours lacking detectable methylation had shorter disease-free survival (DFS)
(P ¼ 0.001, HR ¼ 2.7) and overall survival (OS) (P ¼ 0.001, HR ¼ 3). The favourable prognostic value of NT5E methylation was
confirmed in oestrogen receptor negative (P ¼ 0.011, HR ¼ 3.27, 95% CI: 1.31–8.12) and in triple negative cases (P ¼ 0.004;
HR ¼ 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 ¼ 0.0016, HR ¼ 5.1, 95% CI: 1.8–14.37) and OS (P ¼ 0.0005,
HR ¼ 7.4, 95% CI: 2.416–23.08).
CONCLUSION: NT5E CpG island methylation is a promising breast cancer biomarker
Date Issued
2012-05-31
Date Acceptance
2012-04-23
Citation
British Journal of Cancer, 2012, 107 (1), pp.75-83
ISSN
1532-1827
Publisher
Cancer Research UK
Start Page
75
End Page
83
Journal / Book Title
British Journal of Cancer
Volume
107
Issue
1
Copyright Statement
© 2012 Cancer Research UK. This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the
license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.
license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
ONCOLOGY
NT5E
breast cancer
metastasis
epigenetics
triple-negative breast cancer
ECTO-5'-NUCLEOTIDASE CD73
GENE-EXPRESSION
PROGNOSTIC-FACTORS
ECTO-5-NUCLEOTIDASE
CELLS
RECURRENCE
METASTASES
MANAGEMENT
APOPTOSIS
MIGRATION
Publication Status
Published