肺泡灌洗液基因甲基化联合癌胚抗原、气道径向超声对肺癌的诊断价值

The valueof SHOX2 and RASSF1A methylation detection in alveolar lavage fluid combined with carcinoembryonic antigen and airway radial ultrasound in the diagnosis of lung cancer

目的探讨肺泡灌洗液(BALF)中矮小同源盒基因2(SHOX2)和RAS相关区域家族1A(RASSF1A)基因甲基化联合癌胚抗原(CEA)、气道径向超声在肺癌诊断的价值。方法选取2019年7月至2020年6月于佛山市第二人民医院就诊经胸部CT提示肺结节或占位患者114例,根据病理诊断确认肺癌62例(肺癌组),肺良性病变52例(对照组)。在气道径向超声定位后收集患者BALF样本、外周静脉血,对BALF样本进行细胞学检查及实时荧光PCR法检测SHOX2和RASSF1A基因甲基化阳性率,对外周静脉血血清CEA水平进行检测。结果肺癌组SHOX2、RASSF1A基因任一甲基化阳性40例(64.52%),阴性22例,对照组任一甲基化阳性2例(3.85%),阴性50例,差异有统计学意义(P<0.05);肿瘤直径与肺泡灌洗液甲基化阳性率呈负相关(P<0.05);23例肺癌患者肺泡灌洗液CEA水平异常20例(86.96%),CEA联合任一甲基化阳性22例(95.65%);17例对照组CEA小于5 ng/ml的12例(70.59%),CEA联合基因甲基化双阴性的11例(64.71%);49例肺癌患者气道径向超声可探及明显回音图像,其中任一基因甲基化阳性34例(71.4%),无探及回音图像有13例,其中基因甲基化阴性8例(38.4%),差异有统计学意义(P<0.05)。结论肺癌组患者经气道径向超声定位后获取的肺泡灌洗液甲基化阳性率更高。肺泡灌洗液SHOX2和RASSF1A基因甲基化联合癌胚抗原、气道径向超声有助于肺癌的早期诊断。

Objective To investigate the value of short homeobox gene 2(SHOX2)and RAS-related region family 1A(RASSF1A)gene methylation detection in broncho alveolar lavage fluid(BALF)combined with carcinoembryonic antigen(CEA)and airway radial ultrasound in the diagnosis of lung cancer.Methods From July 2019 to June 2020,114 patients with pulmonary nodules or mass detected by chest CT in our hospital were selected.According to pathological diagnosis,62 patients with lung cancer(lung cancer group)and 52 patients with benign lung lesions(control group)were confirmed.After radial ultrasound positioning of the airway,BALF samples were collected.Peripheral venous blood was also collected.The BALF samples were subjected to cytological examination and real-time fluorescent PCR method to detect the positive methylation rates of SHOX2 and RASSF1A genes.CEA levels in peripheral venous blood were also measured.Results In the lung cancer group,40 cases(64.52%)were positive for any methylation of SHOX2 and RASSF1A genes,and 22 cases were negative methylation.In contrast,there were only 2 cases(3.85%)of positive methylation of any gene in the control group,and 50 cases of negative methylation.The difference between the two groups was statistically significant(P<0.05).The tumor diameter was negatively correlated with the positive rate of methylation in BALF(P<0.05).In 23 lung cancer patients,there were 20 cases(86.96%)with abnormal CEA level and 22 cases(96.65%)with any methylation positive combined high level of CEA.In 17 controls,there were 12 cases(70.59%)with CEA less than 5ng/ml,and 11 cases(64.71%)with double negative gene methylation combined low levels of CEA.There were 49 lung cancer patients had obvious echogenic images detected by radial ultrasound,of which 34(71.4%)were positive for any gene methylation,and 13(38.4%)were not detected by echogenic images,of which 8(38.4%)were negative for gene methylation(P<0.05).Conclusions The positive rate of methylation of BALF collected by radial ultrasound navigated is higher in lung cancer patients.Alveolar lavage solution SHOX2 and RASSF1A gene methylation combined with CEA and airway radial ultrasound are helpful for early diagnosis of lung cancer.