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低剂量CT联合血浆矮小同源盒基因2、Ras相关区域家族1A、前列腺素E受体4基因甲基化对恶性肺结节的诊断价值

Diagnostic value of low-dose CT combined with plasma short stature homeobox 2, Ras association domain family 1A and prostaglandin E receptor 4 gene methylation for malignant pulmonary nodules

    摘要
  • 摘要:
    目的 探讨血浆矮小同源盒基因2(SHOX2)、Ras相关区域家族1A(RASSF1A)、前列腺素E受体4(PTGER4)基因甲基化检测联合低剂量CT(LDCT)对恶性肺结节的诊断价值。
    方法 选取153例拟行手术治疗的肺结节住院患者作为研究对象，检测患者血浆目标基因SHOX2、RASSF1A、PTGER4及内参基因ACTB的Ct值，进一步计算各基因的ΔCt值(即Ct目标基因-Ct内参基因)和三基因拟合阳性指数(PI)。分析ΔCt值、三基因拟合PI作为甲基化阳性判定标准时诊断恶性肺结节的敏感度及特异度; 绘制受试者工作特征(ROC)曲线，评估LDCT联合基因甲基化检测对恶性肺结节的诊断价值。
    结果 根据病理结果，将患者分为良性肺结节组47例和恶性结节组106例。三基因拟合PI诊断恶性肺结节的敏感度为58.49%, 特异度为70.21%; ΔCtSHOX2值、ΔCtRASSF1A值、ΔCtPTGER4值单独及联合诊断恶性肺结节的敏感度分别为33.96%、43.40%、49.06%及75.47%, 特异度分别为87.23%、72.34%、80.85%及100.00%; 相较于三基因拟合PI, ΔCt值更适用于肺结节良恶性的鉴别诊断。基于病理诊断结果, LDCT诊断、基因甲基化联合LDCT诊断的恶性肺结节阳性率差异有统计学意义(P＜0.001)。ROC曲线分析结果显示，血浆SHOX2、RASSF1A、PTGER4基因甲基化ΔCt值和LDCT单独及联合诊断恶性肺结节的曲线下面积分别为0.604、0.582、0.629、0.668及0.981, 联合指标的诊断价值高于单一指标。
    结论 LDCT联合血浆SHOX2、RASSF1A、PTGER4基因甲基化检测对恶性肺结节具有较高的诊断效能，可显著降低LDCT在早期肺癌筛查中的假阳性率。

     

    Abstract:
    Objective To investigate the diagnostic value of plasma short stature homeobox 2 (SHOX2), Ras association domain family 1A (RASSF1A) and prostaglandin E receptor 4 (PTGER4) gene methylation detection combined with low-dose CT (LDCT) for malignant pulmonary nodules.
    Methods A total of 153 hospitalized patients with pulmonary nodules scheduled for surgical treatment were selected as study subjects. The Ct values of the target genes SHOX2, RASSF1A, PTGER4 and the internal reference gene ACTB in the patients' plasma were detected, and the ΔCt values (ΔCttarget gene -Ctinternal reference gene) and the three-gene fitting positive index (PI) of each gene were further calculated. The sensitivity and specificity of ΔCt values and the three-gene fitting PI as methylation-positive diagnostic criteria for malignant pulmonary nodules were analyzed. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic value of LDCT combined with gene methylation detection for malignant pulmonary nodules.
    Results According to the pathological results, the patients were divided into benign pulmonary nodule group (47 cases) and malignant nodule group (106 cases). The sensitivity and specificity of the three-gene fitting PI for diagnosing malignant pulmonary nodules were 58.49% and 70.21%, respectively. The sensitivities of ΔCtSHOX2, ΔCtRASSF1A and ΔCtPTGER4 values for diagnosing malignant pulmonary nodules alone and their combination were 33.96%, 43.40%, 49.06% and 75.47%, respectively, and the specificities were 87.23%, 72.34%, 80.85% and 100.00%, respectively. Compared with the three-gene fitting PI, ΔCt values were more suitable for the differential diagnosis of benign and malignant pulmonary nodules. Based on the pathological diagnosis results, there was a statistically significant difference in the positive rates of malignant pulmonary nodules between LDCT diagnosis and gene methylation combined with LDCT diagnosis (P < 0.001). ROC curve analysis showed that the areas under the curves (AUCs) for diagnosing malignant pulmonary nodules using plasma SHOX2, RASSF1A, PTGER4 gene methylation ΔCt values, LDCT alone, and their combination were 0.604, 0.582, 0.629, 0.668 and 0.981, respectively. The diagnostic value of the combined indicators was higher than that of single indicators.
    Conclusion LDCT combined with plasma SHOX2, RASSF1A, PTGER4 gene methylation detection has high diagnostic efficacy for malignant pulmonary nodules and can significantly reduce the false-positive rate of LDCT in early screening of lung cancer.

     

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