Sox17 Promoter Methylation in Plasma DNA Is Associated With Poor Survival and Can Be Used as a Prognostic Factor in Breast Cancer. Issue 11 (March 2015)

• Record Type: Journal Article
• Authors: Fu, Deyuan; Ren, Chuanli; Tan, Haosheng; Wei, Jinli; Zhu, Yuxiang; He, Chunlan; Shao, Wenxi; Zhang, Jiaxin; Pezzilli., Raffaele
• Is Part Of: Medicine. Volume 94:Issue 11(2015)
• Publication Date: 2015-03
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000000637
• Languages: English
• ISSNs: 0025-7974

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Abstract</title> <p>Aberrant DNA methylation that leads to the inactivation of tumor suppressor genes is known to play an important role in the development and progression of breast cancer. Methylation status of cancer-related genes is considered to be a promising biomarker for the early diagnosis and prognosis of tumors. This study investigated the methylation status of the <italic>Sox17</italic> gene in breast cancer tissue and its corresponding plasma DNA to evaluate the association of methylation levels with clinicopathological parameters and prognosis.</p> <p>The methylation status of the <italic>Sox17</italic> gene promoter was evaluated with methylation-specific polymerase chain reaction (MSP) in 155 paired breast cancer tissue and plasma samples and in 60 paired normal breast tissue and plasma samples. Association of <italic>Sox17</italic> methylation status with clinicopathological parameters was analyzed by χ<sup>2</sup> tests. Overall and disease-free survival (DFS) curves were calculated using Kaplan–Meier analysis, and the differences between curves were analyzed by log-rank tests.</p> <p>The frequency of <italic>Sox17</italic> gene methylation was 72.9% (113/155) in breast cancer tissues and 58.1% (90/155) in plasma DNA. <italic>Sox17</italic> gene methylation was not found in normal breast tissues or in their paired plasma DNA. There was a significant correlation of <italic>Sox17</italic> methylation between corresponding tumor tissues and paired plasma DNA (<italic>r</italic> = 0.688, <italic>P</italic> < 0.001). Aberrant <italic>Sox17</italic> methylation in cancer tissues and in plasma DNA was significantly associated with the tumor node metastasis stage (<italic>P</italic> = 0.035 and <italic>P</italic> <italic>=</italic> 0.001, respectively) and with lymph node metastasis (<italic>P</italic> < 0.001 and <italic>P</italic> <italic>=</italic> 0.001, respectively). Kaplan–Meier survival curves showed that aberrant <italic>Sox17</italic> promoter methylation in cancer tissues and plasma DNA was associated with poor DFS (<italic>P</italic> < 0.005) and overall survival (OS) (<italic>P</italic> < 0.005). Multivariate analysis showed that <italic>Sox17</italic> methylation in plasma DNA was an independent prognostic factor in breast cancer for both DFS (<italic>P</italic> = 0.020; hazard ratio [HR] = 2.142; 95% confidence interval [CI]: 1.128–4.067) and for OS (<italic>P</italic> = 0.001; HR = 4.737; 95% CI: 2.088–10.747).</p> <p> <italic>Sox17</italic> gene promoter methylation may play an important role in breast cancer progression and could be used as a prognostic biomarker to identify patients at risk of developing metastasis or recurrence after mastectomy.</p> </sec> </abstract>