Lung cancer tumorigenesis is mainly due to accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic alteration is more frequent than somatic mutation in lung cancer. CpG island methylation of homeobox-associated genes is commonly seen in most early stage tumors. This study aimed at examining the potential usefulness of DNA methylation biomarker SHOX2, in broncho-alveolar lavage, in the diagnosis of lung cancer. Broncho-alveolar lavage was obtained from 80 patients; 60 cases with lung masses (proved malignant by histopathology) and 20 age and gender matched patients with benign lung lesions (benign controls). SHOX2 methylation status was evaluated using methylation analysis by restriction endonuclease digestion and real-time PCR. SHOX2 methylation level ranged 3.90–77.16% in cases, and 3.52–7.86% in controls, (p ≤ 0.001). SHOX2 methylation levels in comparison to tissue biopsy pathology (the gold standard test) had 76.92% sensitivity, 70% specificity, 87% positive predictive value, and 53.8% negative predictive value in diagnosing lung cancer. Different methylation levels were noted in different lung pathologies, (p = 0.003), with the highest methylation levels in squamous cell carcinoma followed by adenocarcinoma and anaplastic carcinoma then lastly carcinoma in situ. SHOX2 methylation levels could differentiate different varieties of lung cancer from benign lung lesions.

中文翻译：

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患有肺癌的埃及人的 SHOX2 基因甲基化

肺癌的发生主要是由于呼吸道上皮中遗传和表观遗传事件的积累。表观遗传改变在肺癌中比体细胞突变更常见。同源盒相关基因的 CpG 岛甲基化在大多数早期肿瘤中很常见。本研究旨在检查支气管肺泡灌洗中 DNA 甲基化生物标志物 SHOX2 在诊断肺癌中的潜在用途。支气管肺泡灌洗液来自 80 名患者；60例肺肿块（经组织病理学证实为恶性）和20例年龄和性别匹配的肺良性病变患者（良性对照）。SHOX2 甲基化状态通过限制性内切酶消化和实时 PCR 使用甲基化分析进行评估。SHOX2 甲基化水平在病例中为 3.90-77.16%，在对照中为 3.52-7.86%，（p ≤ 0。001）。与组织活检病理学（金标准测试）相比，SHOX2 甲基化水平在诊断肺癌方面具有 76.92% 的敏感性、70% 的特异性、87% 的阳性预测值和 53.8% 的阴性预测值。在不同的肺病理中注意到不同的甲基化水平（p = 0.003），鳞状细胞癌的甲基化水平最高，其次是腺癌和间变性癌，最后是原位癌。SHOX2 甲基化水平可以区分不同种类的肺癌和良性肺部病变。在不同的肺病理中注意到不同的甲基化水平（p = 0.003），鳞状细胞癌的甲基化水平最高，其次是腺癌和间变性癌，最后是原位癌。SHOX2 甲基化水平可以区分不同种类的肺癌和良性肺部病变。在不同的肺病理中注意到不同的甲基化水平（p = 0.003），鳞状细胞癌的甲基化水平最高，其次是腺癌和间变性癌，最后是原位癌。SHOX2 甲基化水平可以区分不同种类的肺癌和良性肺部病变。