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Abstract：
BACKGROUND: Lung adenocarcinoma (LUAD) represents the most prevalent type of lung cancer. SHOX2 and RASSF1A methylation have been identified as important biomarkers for diagnosis and prognosis of lung cancer. Bronchoalveolar lavage fluid (BALF) exhibits good specificity and sensitivity in diagnosing pulmonary diseases, but its acquisition is challenging and may cause discomfort to patients. In clinical, plasma samples are more convenient to obtain than BALF; however, there is little research on the concurrent detection of SHOX2 and RASSF1A methylation in plasma. This study aims to assess the diagnostic value of a combined promoter methylation assay for SHOX2 and RASSF1A in early-stage LUAD using plasma samples.
METHODS: BALF and blood samples were obtained from 36 early-stage LUAD patients, with a control group of nineteen non-tumor individuals. The promoter methylation levels of SHOX2 and RASSF1A in all subjects were assessed using the human SHOX2 and RASSF1A gene methylation kit.
RESULTS: The methylation detection rate of SHOX2 and RASSF1A in plasma was 61.11%, slightly lower than that in BALF (66.7%). The Chi-square test revealed no significant difference in the methylation rate between BALF and plasma (P > 0.05). The area under the receiver operating characteristic (ROC) curve analysis for blood was 0.806 (95% CI, 0.677 to 0.900), while for BALF it was 0.781 (95% CI, 0.649 to 0.881). Additionally, we conducted an analysis on the correlation between SHOX2 and RASSF1A methylation levels in plasma with gender, age, tumor differentiation, pathologic classification, and other clinicopathological variables; however, no significant correlations were observed.
CONCLUSIONS: Measurement of SHOX2 and RASSF1A methylation for early diagnosis of LUAD can be achieved with high sensitivity and specificity by using plasma as a substitute for BALF samples.
METHODS: BALF and blood samples were obtained from 36 early-stage LUAD patients, with a control group of nineteen non-tumor individuals. The promoter methylation levels of SHOX2 and RASSF1A in all subjects were assessed using the human SHOX2 and RASSF1A gene methylation kit.
RESULTS: The methylation detection rate of SHOX2 and RASSF1A in plasma was 61.11%, slightly lower than that in BALF (66.7%). The Chi-square test revealed no significant difference in the methylation rate between BALF and plasma (P > 0.05). The area under the receiver operating characteristic (ROC) curve analysis for blood was 0.806 (95% CI, 0.677 to 0.900), while for BALF it was 0.781 (95% CI, 0.649 to 0.881). Additionally, we conducted an analysis on the correlation between SHOX2 and RASSF1A methylation levels in plasma with gender, age, tumor differentiation, pathologic classification, and other clinicopathological variables; however, no significant correlations were observed.
CONCLUSIONS: Measurement of SHOX2 and RASSF1A methylation for early diagnosis of LUAD can be achieved with high sensitivity and specificity by using plasma as a substitute for BALF samples.
摘要：
背景：肺腺癌（LUAD）是最常见的肺癌类型。SHOX2和RASSF1A甲基化已被确定为肺癌诊断和预后的重要生物标志物。支气管肺泡灌洗液（BALF）在肺部疾病诊断中具有良好的特异性和敏感性，但它的获取是具有挑战性的，并可能导致不适的病人。在临床上，血浆样品比BALF更容易获得；然而，关于同时检测血浆中SHOX2和RASSF1A甲基化的研究很少。本研究旨在使用血浆样本评估SHOX2和RASSF1A联合启动子甲基化检测在早期LUAD中的诊断价值。
方法：收集36例早期LUAD患者的BALF和血液样本，与19个非肿瘤个体的对照组。使用人SHOX2和RASSF1A基因甲基化试剂盒评估所有受试者中SHOX2和RASSF1A的启动子甲基化水平。
结果：血浆中SHOX2和RASSF1A的甲基化检出率为61.11%，略低于BALF（66.7%）。卡方检验显示BALF与血浆间甲基化率差异无统计学意义(P>0.05)。血液的受试者工作特征（ROC）曲线分析下面积为0.806（95％CI，0.677至0.900），而BALF为0.781（95%CI，0.649至0.881）。此外,我们对血浆中SHOX2和RASSF1A甲基化水平与性别的相关性进行了分析,年龄,肿瘤分化，病理分类，和其他临床病理变量；然而，没有观察到显著的相关性。
结论：使用血浆替代BALF样本，可以高灵敏度和特异性地测量SHOX2和RASSF1A甲基化以早期诊断LUAD。
方法：收集36例早期LUAD患者的BALF和血液样本，与19个非肿瘤个体的对照组。使用人SHOX2和RASSF1A基因甲基化试剂盒评估所有受试者中SHOX2和RASSF1A的启动子甲基化水平。
结果：血浆中SHOX2和RASSF1A的甲基化检出率为61.11%，略低于BALF（66.7%）。卡方检验显示BALF与血浆间甲基化率差异无统计学意义(P>0.05)。血液的受试者工作特征（ROC）曲线分析下面积为0.806（95％CI，0.677至0.900），而BALF为0.781（95%CI，0.649至0.881）。此外,我们对血浆中SHOX2和RASSF1A甲基化水平与性别的相关性进行了分析,年龄,肿瘤分化，病理分类，和其他临床病理变量；然而，没有观察到显著的相关性。
结论：使用血浆替代BALF样本，可以高灵敏度和特异性地测量SHOX2和RASSF1A甲基化以早期诊断LUAD。
