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.
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机译:肺腺癌是恶性胸腔积液(MPE)的最常见原因之一。 MPE的存在预后不良。尽管表观遗传学改变通常与人类瘤形成有关,但MPE患者的病因稀少。我们旨在评估胸水中抑癌基因DNA甲基化的预后价值。前瞻性纳入了30例因肺腺癌引起的MPE患者。甲基化特异性(MS)PCR用于研究胸水中抑癌基因p16 / INK4a,MGMT,BRCA1和RARβ的启动子区域的甲基化状态。收集临床数据和生存率。使用Kaplan-Meier图和Cox回归进行生存分析。在25例患者中检测到至少一个基因的甲基化过高(83.3%)。在与较短生存期显着相关的多元分析因素上,任何研究的基因均缺乏高甲基化(危险比= 9.3; p = 0.001),查尔森指数≥3(危险比= 9.6,p = 0.002)和未进行肿瘤治疗(危险比= 11.1; p <0.001)。肿瘤抑制基因异常启动子甲基化的分析可能有助于预测预后,但是需要进一步的研究来验证我们的发现。
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