Application of SHOX2 and APC Methylation Combined with SCC and CYFRA21-1 in the Early Diagnostic of Lung Cancer

ZHANG Heng; QIAN Rulin; QU Ge

doi:10.3969/j.issn.1004-437X.2025.23.012

Abstract：Objective To investigate the value of short stature homobox2(SHOX2)and adenomatous polyposis coli(APC)methylation combined with squamous cell carcinoma antigen(SCC)and cytokeratin 19 soluble fragment(CYFRA21-1)in the early diagnosis of lung cancer.Methods From January 2021 to July 2022,whole blood samples were collected from 55 patients with lung cancer(lung cancer group)and 60 patients with benign lung diseases(control group)who received medical treatment at Henan Provincial Chest Hospital.The methylation of SHOX2 and APC genes was detected by Real-time PCR,and SCC and CYFRA21-1 were detected by chemiluminescence.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic performance of relevant indicators alone or combined in the early detection of lung cancer.Results The positive rates of SHOX2 and APC gene methylation observed in the lung cancer group were 54.5％(30 out of 55)and 30.9％(17 out of 55),respectively.These rates were markedly higher than those noted in the control group,which were 8.3％(5 out of 60)and 3.3％(2 out of 60).The differences between the two groups were statistically significant(P＜0.001).Meanwhile,in the lung cancer group,the positive rates for serum SCC and CYFRA21-1 were significantly higher compared to the control group.SHOX2 and APC double gene methylation was highly sensitive to adenocarcinoma of the lung,but relatively low to lung squamous cell carcinoma and small cell lung cancer;SCC and CYFRA21-1 were highly sensitive to squamous cell carcinoma of the lung and relatively low to adenocarcinoma of the lung.The combination of the four significantly improved the overall sensitivity,with specificity still greater than 80％.Conclusion The combined detection of SHOX2,APC gene methylation,SCC,CYFRA21-1 levels can improve the sensitivity of the diagnosis of lung cancer patients,and is expected to become a combined detection scheme for the early diagnosis of lung cancer.