NT5E CpG island methylation is a favourable breast cancer biomarker.
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).


CONCLUSIONS
NT5E CpG island methylation is a promising breast cancer biomarker.
Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S. Croce General Hospital, Cuneo, Italy.
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C
Lo Nigro
M
M
Monteverde
S
S
Lee
L
L
Lattanzio
D
D
Vivenza
A
A
Comino
N
N
Syed
A
A
McHugh
H
H
Wang
C
C
Proby
O
O
Garrone
M
M
Merlano
E
E
Hatzimichael
E
E
Briasoulis
O
O
Gojis
C
C
Palmieri
L
L
Jordan
P
P
Quinlan
A
A
Thompson
T
T
Crook
D015720:5'-Nucleotidase / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D015720:5'-Nucleotidase; C548241:NT5E protein, human