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SOX11 的启动子高甲基化与人类前列腺癌的不良临床病理特征相关。

Promoter hypermethylation of SOX11 correlates with adverse clinicopathological features of human prostate cancer.

机构信息

Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

出版信息

Int J Exp Pathol. 2017 Dec;98(6):341-346. doi: 10.1111/iep.12257. Epub 2018 Jan 8.

Abstract

Currently available tools for early diagnosis and prognosis of prostate cancer lack sufficient accuracy. There is a need to identify novel biomarkers for this common malignancy. SOX family genes play an important role in embryogenesis and are also implicated in various cancers. SOX11 has been recently recognized as a potential tumour suppressor that is downregulated in prostate cancer. We hypothesized that hypermethylation may be responsible for SOX11 silencing in human prostate cancer. The aim of the study was to investigate SOX11 promoter methylation in prostate adenocarcinoma by comparing it with benign prostatic hyperplasia (BPH). A total of 143 human prostate tissue samples, 62 from patients with prostate cancer and 81 from patients with BPH were examined by methylation-specific PCR. Associations between SOX11 promoter methylation and clinicopathological parameters were assessed by univariate statistics. Detection rates of SOX11 promoter methylation were 80.6% and 35.8% in prostate cancer and BPH respectively (P < 0.001). SOX11 hypermethylation was associated with adverse clinicopathological characteristics of prostate cancer, including higher PSA level (P < 0.01), Gleason score ≥ 7 (P = 0.03) and perineural invasion (P = 0.03). SOX11 methylation was positively correlated with the PSA level (P = 0.001). Our data indicated that SOX11 can be a promising methylation marker candidate for differential diagnosis and risk stratification for prostate cancer.

摘要

目前用于前列腺癌早期诊断和预后的工具准确性不足。需要鉴定这种常见恶性肿瘤的新型生物标志物。SOX 家族基因在胚胎发生中发挥重要作用,并且与各种癌症相关。SOX11 最近被认为是一种潜在的肿瘤抑制因子,在前列腺癌中下调。我们假设甲基化可能是导致人类前列腺癌中 SOX11 沉默的原因。本研究的目的是通过比较良性前列腺增生(BPH)来研究前列腺腺癌中 SOX11 启动子甲基化。通过甲基化特异性 PCR 共检测了 143 个人类前列腺组织样本,其中 62 例来自前列腺癌患者,81 例来自 BPH 患者。通过单变量统计评估 SOX11 启动子甲基化与临床病理参数之间的关系。前列腺癌和 BPH 中 SOX11 启动子甲基化的检出率分别为 80.6%和 35.8%(P<0.001)。SOX11 高甲基化与前列腺癌的不良临床病理特征相关,包括较高的 PSA 水平(P<0.01)、Gleason 评分≥7(P=0.03)和神经周围侵犯(P=0.03)。SOX11 甲基化与 PSA 水平呈正相关(P=0.001)。我们的数据表明,SOX11 可以成为前列腺癌鉴别诊断和风险分层的有前途的甲基化标记候选物。

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