A prediction model based on DNA methylation biomarkers and radiological characteristics for identifying malignant from benign pulmonary nodules.
BACKGROUND
Lung cancer remains the leading cause of cancer deaths across the world. Early detection of lung cancer by low-dose computed tomography (LDCT) can reduce the mortality rate. However, making a definitive preoperative diagnosis of malignant pulmonary nodules (PNs) found by LDCT is a clinical challenge. This study aimed to develop a prediction model based on DNA methylation biomarkers and radiological characteristics for identifying malignant pulmonary nodules from benign PNs.


METHODS
We assessed three DNA methylation biomarkers (PTGER4, RASSF1A, and SHOX2) and clinically-relevant variables in a training cohort of 110 individuals with PNs. Four machine-learning-based prediction models were established and compared, including the K-nearest neighbors (KNN), random forest (RF), support vector machine (SVM), and logistic regression (LR) algorithms. Variables of the best-performing algorithm (LR) were selected through stepwise use of Akaike's information criterion (AIC). The constructed prediction model was compared with the methylation biomarkers and the Mayo Clinic model using the non-parametric approach of DeLong et al. with the area under a receiver operator characteristic curve (AUC) analysis.


RESULTS
A prediction model was finally constructed based on three DNA methylation biomarkers and one radiological characteristic for identifying malignant from benign PNs. The developed prediction model achieved an AUC value of 0.951 in malignant PNs diagnosis, significantly higher than the three DNA methylation biomarkers (0.912, 95% CI:0.843-0.958, p = 0.013) or Mayo Clinic model (0.823, 95% CI:0.739-0.890, p = 0.001). Validation of the prediction model in the testing cohort of 100 subjects with PNs confirmed the diagnostic value.


CONCLUSION
We have shown that integrating DNA methylation biomarkers and radiological characteristics could more accurately identify lung cancer in subjects with CT-found PNs. The prediction model developed in our study may provide clinical utility in combination with LDCT to improve the over-all diagnosis of lung cancer.
['Xing|Wenqun|W|', 'Sun|Haibo|H|', 'Yan|Chi|C|', 'Zhao|Chengzhi|C|', 'Wang|Dongqing|D|', 'Li|Mingming|M|', 'Ma|Jie|J|http://orcid.org/0000-0001-5346-8457']
D000328:Adult D000368:Aged D014408:Biomarkers, Tumor D001706:Biopsy D016022:Case-Control Studies D019175:DNA Methylation D003937:Diagnosis, Differential D005240:Feasibility Studies D005260:Female D018398:Homeodomain Proteins D006801:Humans D008168:Lung D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D008957:Models, Genetic D055613:Multiple Pulmonary Nodules D012372:ROC Curve D058309:Receptors, Prostaglandin E, EP4 Subtype D014057:Tomography, X-Ray Computed D025521:Tumor Suppressor Proteins
DNA methylation Biomarkers Pulmonary nodules Lung cancer CT