Diagnostic value of serum SHOX2,RASSF1A,and PTGER4 methylation levels in the benign and malignant nature of isolated pulmonary nodules and pathologic staging
QI Qingbin
SU Haitao
HU Jigang
ZHANG Wenxian
GAO Fengxia
JIA Liting
Abstract：Objective To investigate the diagnostic value of methylation levels of the short stature homobox 2(SHOX2)gene,RAS association domain family 1A(RASSF1A),and prostaglandin E receptor 4 gene(PTGER4)in serum free acellular DNA in the diagnosis of benign and malignant solitary pulmonary nodules(SPN).Methods A total of 118 SPN patients admitted to the Affiliated Hospital of Hebei University of Engineering from June 2021 to February 2024 were selected and divided into malignant group(76 cases)and benign group(42 cases)based on pathological diagnosis results.General information of patients in both groups was collected.The serum levels of SHOX2,RASSF1A,PTGER4 gene methylation,and some tumor markers were compared between two groups.Comparison of serum SHOX2,RASSF1A,and PTGER4 gene methylation levels was conducted in different pathologic subtypes of the malignant group.Multivariate logistic regression was applied to analyze the influencing factors of malignant SPN.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum SHOX2,RASSF1A,and PTGER4 gene methylation levels for malignant SPN.Results The methylation levels of SHOX2,RASSF1A,and PTGER4 genes in the malignant group were higher than those in the benign group,and the serum levels of CEA,NSE,SCC,and Cyfra21-1 were higher than those in the benign group(P＜0.05).There were differences in the methylation levels of serum SHOX2,RASSF1A,and PTGER4 genes in the malignant group with different pathologic subtypes(P＜0.05).Regression analysis showed that serum SHOX2,RASSF1A,PTGER4 gene methylation levels,and serum SCC were influencing factors for the occurrence of malignant SPN(P＜0.05).The combined diagnosis of serum SHOX2,RASSF1A,and PTGER4 methylation levels had a higher AUC than SHOX2 methylation levels alone(Z=2.120,P=0.034),RASSF1A methylation levels alone(Z=2.040,P=0.041),and PTGER4 methylation levels alone(Z=2.098,P=0.036).Conclusion The methylation levels of SHOX2,RASSF1A,and PTGER4 genes in serum of patients with malignant SPN are elevated,and the combination of three tests may help diagnose malignant SNPs.
Keywords：Short stature homobox2RAS association domain family 1AProstaglandin E receptor 4 geneMethylationSolitary pulmonary nodulesDiagnostic value
Publication Date：2025-08-28
Online Publishing Date：2025-09-18(First online date of this platform, not the publication date of the document)
Pages：6( 1010-1015 )