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首页> 外文期刊>Clinical epigenetics. >Diagnostic and prognostic value of SHOX2 and SEPT9 DNA methylation and cytology in benign, paramalignant, and malignant ascites
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Diagnostic and prognostic value of SHOX2 and SEPT9 DNA methylation and cytology in benign, paramalignant, and malignant ascites

机译：SHOX2和SEPT9 DNA甲基化和细胞学检查对良性，副恶性和恶性腹水的诊断和预后价值

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BackgroundCytology remains the gold standard for the detection of malignant cells in ascites. However, its sensitivity is limited. The aim of this study was to evaluate DNA methylation biomarkers for the differential diagnosis of benign (ascites in patients without malignancy), malignant (ascites in cancer patients directly caused by malignancy), and paramalignant (ascites in cancer patients caused by comorbidities but not by malignancy) ascites. MethodsA cohort of 283 patients (134 cancer patients, 149 patients with benign diseases) presenting with ascites was prospectively enrolled. Ascites was evaluated by means of cytopathological investigation and DNA methylation of SHOX2 and SEPT9 in the cell-free and cellular fraction. DNA methylation in bisulfite-converted DNA was determined using quantitative methylation specific real-time PCR. Cytopathological and DNA methylation results were evaluated with regard to diagnosis and overall survival (OS). ResultsPatients with positive DNA methylation had a poor overall survival compared to methylation-negative patients (hazard ratio: HR?=?1.97, p =?0.001). In multivariate survival analysis, DNA methylation was an independent prognostic parameter ( p =?0.003) together with age (HR?=?1.03, p The combination of methylation with cytopathological analyses led to a 42?% increase in the detection rate of malignant ascites, resulting in 37?% positively diagnosed cancer patients and a specificity of 97?%. Among cancer patients, patients with DNA methylation-positive ascites showed an adverse clinical course (HR?=?1.63, p =?0.039). ConclusionsDNA methylation testing adds diagnostic and prognostic information and might constitute an effective ancillary method for the differential diagnosis of malignant, paramalignant, and benign ascites.
机译：背景细胞学仍然是检测腹水中恶性细胞的金标准。但是，其灵敏度是有限的。这项研究的目的是评估DNA甲基化生物标志物，以鉴别诊断良性（无恶性肿瘤患者的腹水），恶性（由恶性肿瘤直接导致的癌症患者腹水）和副恶性（由合并症引起而不由合并症引起的腹水）恶性）腹水。方法前瞻性纳入283例表现为腹水的患者（134例癌症患者，149例良性疾病）。通过细胞病理学研究以及无细胞和细胞级分中SHOX2和SEPT9的DNA甲基化来评估腹水。使用定量甲基化特异性实时PCR测定亚硫酸氢盐转化的DNA中的DNA甲基化。评估了细胞病理学和DNA甲基化结果的诊断和总生存期（OS）。结果与甲基化阴性的患者相比，DNA甲基化阳性的患者的总生存期较差（危险比：HR≥1.97，p = 0.001）。在多变量生存分析中，DNA甲基化与年龄（HR = 1.03，p）是一个独立的预后参数（p = 0.003），甲基化与细胞病理学分析相结合可将恶性腹水的检出率提高42％。 DNA甲基化阳性腹水患者的临床病程较差（HR≥1.63，p≤0.039），导致37％的癌症患者被诊断为阳性，特异性为97％。增加了诊断和预后信息，可能构成鉴别恶性，副恶性和良性腹水的有效辅助方法。

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