Identification of Specific Candidate Diagnostic Biomarkers for Lung Squamous Cell Carcinoma Based on Methylation

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.