NT5E CpG island methylation is a favourable breast cancer biomarker. / 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.
In: British Journal of Cancer, Vol. 107, No. 1, 2012, p. 75-83.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - NT5E CpG island methylation is a favourable breast cancer biomarker
A1 - Lo Nigro,C.
A1 - Monteverde,M.
A1 - Lee,S.
A1 - Lattanzio,L.
A1 - Vivenza,D.
A1 - Comino,A.
A1 - Syed,N.
A1 - McHugh,A.
A1 - Wang,H.
A1 - Proby,C.
A1 - Garrone,O.
A1 - Merlano,M.
A1 - Hatzimichael,E.
A1 - Briasoulis,E.
A1 - Gojis,O.
A1 - Palmieri,C.
A1 - Jordan,L.
A1 - Quinlan,P.
A1 - Thompson,A.
A1 - Crook,T.
AU - Lo Nigro,C.
AU - Monteverde,M.
AU - Lee,S.
AU - Lattanzio,L.
AU - Vivenza,D.
AU - Comino,A.
AU - Syed,N.
AU - McHugh,A.
AU - Wang,H.
AU - Proby,C.
AU - Garrone,O.
AU - Merlano,M.
AU - Hatzimichael,E.
AU - Briasoulis,E.
AU - Gojis,O.
AU - Palmieri,C.
AU - Jordan,L.
AU - Quinlan,P.
AU - Thompson,A.
AU - Crook,T.
PY - 2012
Y1 - 2012
N2 - 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. © 2012 Cancer Research UK All rights reserved.
AB - 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. © 2012 Cancer Research UK All rights reserved.
UR - http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-84863004265&md5=36f0166d54ba62971e3aa9c1e9c6c2a5
U2 - 10.1038/bjc.2012.212
DO - 10.1038/bjc.2012.212
M1 - Article
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 1
VL - 107
SP - 75
EP - 83
ER -