Methylated DNA and high total DNA levels in the serum of patients with breast cancer following neoadjuvant chemotherapy are predictive of a poor prognosis

Fujita,Noriko; Kagara,Naofumi; Yamamoto,Noriaki; Shimazu,Kenzo; Shimomura,Atsushi; Shimoda,Masafumi; Maruyama,Naomi; Naoi,Yasuto; Morimoto,Koji; Oda,Naofumi; Kim,Seung Jin; Noguchi,Shinzaburo

doi:10.3892/ol.2014.2068

Methylated DNA and high total DNA levels in the serum of patients with breast cancer following neoadjuvant chemotherapy are predictive of a poor prognosis

Authors:
- Noriko Fujita
- Naofumi Kagara
- Noriaki Yamamoto
- Kenzo Shimazu
- Atsushi Shimomura
- Masafumi Shimoda
- Naomi Maruyama
- Yasuto Naoi
- Koji Morimoto
- Naofumi Oda
- Seung Jin Kim
- Shinzaburo Noguchi
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Affiliations: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita‑shi, Osaka 565‑0871, Japan, Central Research Laboratories, Sysmex Corporation, Kobe 651-2271, Japan
Published online on: April 15, 2014 https://doi.org/10.3892/ol.2014.2068
Pages: 397-403

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Abstract

In a previous study, we established a one‑step methylation‑specific polymerase chain reaction (OS‑MSP) assay for the detection of methylated DNA (met‑DNA) and total DNA levels in serum. For the present study, this OS‑MSP assay was used for patients with breast cancer treated with neoadjuvant chemotherapy (NAC) in order to investigate the prognostic significance of met‑DNA and total DNA levels. Following treatment with NAC and prior to surgery, serum samples obtained from 120 patients with stage II/III breast cancer were subjected to the OS‑MSP assay for analysis of the glutathione S‑transferase pi 1, Ras association (RalGDS/AF‑6) domain family member 1 and retinoic acid receptor β2 genes. The detection of methylation in a minimum of one of these genes indicated a positive outcome of the assay. The total DNA content of the serum was also determined. Of the 120 stage II/III patients, seven (6%) were positive for met‑DNA in serum and showed a significantly worse overall survival (OS) time compared with patients negative for met‑DNA (n=113) (5‑year OS, 43 vs. 85%; P=0.002). The patients with high total DNA levels in serum (n=40) also showed a significantly worse OS compared with those with low total DNA levels (n=80) (65 vs. 91%; P<0.001). The presence of met‑DNA and high total DNA levels in the serum were found to be significant prognostic factors that are independent of a pathological complete response by multivariate analysis. Following NAC, met‑DNA and high total DNA levels in the serum detected with the OS‑MSP assay constitute novel prognostic factors for patients with breast cancer; this may be clinically useful for the prognosis prediction for patients who do not achieve a pathological complete response following NAC.

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