Detection of the DNA Methylation of Seven Genes Contribute to the Early Diagnosis of Lung Cancer

Background: Low-dose Computed Tomography (CT) is used for the detection of pulmonary nodules, but the ambiguous risk evaluation causes overdiagnosis. Here, we explored the significance of the DNA methylation of 7 genes including TAC1, CDO1, HOXA9, ZFP42, SOX17, RASSF1A and SHOX2 in the blood cfDNA samples in distinguishing lung cancer from benign nodules and healthy individuals.

Method: A total of 149 lung cancer patients [72 mass and 77 ground-glass nodules (GGNs)], 5 benign and 48 healthy individuals were tested and analyzed in this study. The lasso-logistic regression model was built for distinguishing cancer and control/healthy individuals or IA lung cancer and non-IA lung cancer cases.

Results: The positive rates of methylation of 7 genes were higher in the cancer group as compared with the healthy group. We constructed a model using age, sex and the ΔCt value of 7 gene methylation to distinguish lung cancer from benign and healthy individuals. The sensitivity, specificity and AUC (area under the curve) were 86.7%, 81.4% and 0.891, respectively. Also, we assessed the significance of 7 gene methylation together with patients' age and sex in distinguishing of GGNs type from the mass type. The sensitivity, specificity and AUC were 77.1%, 65.8% and 0.753, respectively. Furthermore, the methylation positive rates of CDO1 and SHOX2 were different between I-IV stages of lung cancer. Specifically, the positive rate of CDO1 methylation was higher in the non-IA group as compared with the IA group.

Conclusion: Collectively, this study reveals that the methylation of 7 genes has a big significance in the diagnosis of lung cancer with high sensitivity and specificity. Also, the 7 genes present with certain significance in distinguishing the GGN type lung cancer, as well as different stages.