Bronchopleural Unit, Respiratory and Infectious Disease Research Group, Pneumology Service of Complexo Hospitalario Universitario de Vigo, Bio-medical Research Institute of Vigo, Vigo, Spain.
Cancer Biol Ther. 2012 Dec;13(14):1436-42. doi: 10.4161/cbt.22004. Epub 2012 Sep 6.
Lung adenocarcinoma is one of the most frequent causes of malignant pleural effusions (MPE). The presence of MPE bears a poor prognosis. Although epigenetic changes are commonly related to human neoplasia, scarce date is available on patients with MPE. We aimed to estimate the prognostic value of DNA methylation of tumor suppressor genes from pleural fluid. Thirty patients with MPE due to lung adenocarcinoma were prospectively included. Methylation-specific (MS) PCR was used to study the methylation status of the promoter region of tumor suppressor genes p16/INK4a, MGMT, BRCA1 and RARβ in pleural fluid. Clinical data and survival were collected. Survival analysis was performed using Kaplan-Meier plots and Cox regression. Hypermethylation in at least one gene was detected in 25 patients (83.3%). On multivariate analysis factors significantly associated with shorter survival were the lack of hypermethylation in any of the studied genes (hazard ratio = 9.3; p = 0.001), Charlson index ≥ 3 (hazard ratio = 9.6, p = 0.002) and no oncological treatment (hazard ratio = 11.1; p < 0.001). Analysis of aberrant promoter hypermethylation of tumor suppressor genes may be useful in predicting prognosis, but further studies are needed to validate our findings.
肺腺癌是导致恶性胸腔积液（MPE）的最常见原因之一。MPE 的存在预示着预后不良。尽管表观遗传改变通常与人类肿瘤有关，但关于 MPE 患者的数据很少。我们旨在评估肿瘤抑制基因 DNA 甲基化在胸腔积液中的预后价值。前瞻性纳入 30 例因肺腺癌导致的 MPE 患者。采用甲基化特异性（MS）PCR 研究胸腔积液中肿瘤抑制基因 p16/INK4a、MGMT、BRCA1 和 RARβ 启动子区域的甲基化状态。收集临床数据和生存情况。采用 Kaplan-Meier 图和 Cox 回归进行生存分析。在 25 例患者（83.3%）中检测到至少一个基因的异常甲基化。多因素分析显示，与生存时间较短相关的因素有：研究的基因中没有任何一个发生高甲基化（风险比=9.3；p=0.001）、Charlson 指数≥3（风险比=9.6，p=0.002）和未进行肿瘤治疗（风险比=11.1；p<0.001）。分析肿瘤抑制基因异常启动子高甲基化可能有助于预测预后，但需要进一步研究来验证我们的发现。
