DNA methylation abnormalities are frequent events in early tumors. DNA methylation is relatively stable over time and can be detected in blood. Therefore, DNA methylation has a great potential to become an early diagnostic biomarker of cancers. To find potential diagnostic markers for lung squamous cell carcinoma (LUSC), a method for identifying LUSC-specific candidate diagnostic markers was proposed. We screened 6 LUSC-specific CpGs by comparing the methylation profiles of 172 samples from LUSC patients, 42 normal lung samples, 1306 samples from patients with other cancers, which was collected from The Cancer Genome Atlas (TCGA) database, and 184 normal blood samples, which was collected from Gene Expression Omnibus (GEO) database. A support vector machine model was built based on the methylation levels of the candidate diagnostic biomarkers, and we optimized the model by sixfold cross-validation. The combination of six sites achieved 93%–99% sensitivity in predicting LUSC, 100% specificity in excluding normal samples, and 99.55% specificity in excluding non-LUSC samples. In addition, a diagnostic model was established by using six LUSC-specific biomarkers, and the sensitivity and specificity of LUSC stage I samples were 95.2% and 99.4%. At the same time, genes for six LUSC-specific CpGs localization are closely related to cancer occurrence, which indicates that six LUSC-specific CpGs can be used as candidate biomarkers for LUSC diagnosis. Overall, our study provides promising biomarkers for the diagnosis of LUSC.

中文翻译：

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基于甲基化的肺鳞状细胞癌的特定候选诊断生物标志物的鉴定。

DNA甲基化异常是早期肿瘤中的常见事件。DNA甲基化随时间推移相对稳定，可以在血液中检测到。因此，DNA甲基化具有成为癌症的早期诊断生物标志物的巨大潜力。为了找到潜在的肺鳞状细胞癌诊断标记，提出了一种识别LUSC特异性候选诊断标记的方法。我们比较了LUSC患者的172个样本，42例正常肺样本，1306例其他癌症患者样本的甲基化谱，筛选了6种LUSC特异性CpGs，这些样本是从癌症基因组图谱（TCGA）数据库中收集的，以及184例正常血液样本，它是从Gene Expression Omnibus（GEO）数据库收集的。根据候选诊断性生物标志物的甲基化水平建立了支持向量机模型，我们通过六重交叉验证对模型进行了优化。六个位点的组合在预测LUSC时达到93％–99％的灵敏度，在排除正常样品时达到100％的特异性，在排除非LUSC样品时达到99.55％的特异性。此外，通过使用六个LUSC特异性生物标记建立了诊断模型，LUSC I期样品的敏感性和特异性分别为95.2％和99.4％。同时，六个LUSC特异性CpGs定位的基因与癌症的发生密切相关，这表明六个LUSC特异性CpGs可以用作LUSC诊断的候选生物标记。总体而言，我们的研究为LUSC的诊断提供了有希望的生物标志物。在排除非LUSC样品中的特异性为99.55％。此外，通过使用六个LUSC特异性生物标记建立了诊断模型，LUSC I期样品的敏感性和特异性分别为95.2％和99.4％。同时，六个LUSC特异性CpGs定位的基因与癌症的发生密切相关，这表明六个LUSC特异性CpGs可以用作LUSC诊断的候选生物标记。总体而言，我们的研究为LUSC的诊断提供了有希望的生物标志物。在排除非LUSC样品中的特异性为99.55％。此外，通过使用六个LUSC特异性生物标记建立了诊断模型，LUSC I期样品的敏感性和特异性分别为95.2％和99.4％。同时，六个LUSC特异性CpGs定位的基因与癌症的发生密切相关，这表明六个LUSC特异性CpGs可以用作LUSC诊断的候选生物标记。总体而言，我们的研究为LUSC的诊断提供了有希望的生物标志物。这表明六个LUSC特异性CpG可用作LUSC诊断的候选生物标记。总体而言，我们的研究为LUSC的诊断提供了有希望的生物标志物。这表明六个LUSC特异性CpG可用作LUSC诊断的候选生物标记。总体而言，我们的研究为LUSC的诊断提供了有希望的生物标志物。