J Korean Med Sci.  2024 Jan;39(2):e28. 10.3346/jkms.2024.39.e28.

Combination Analysis of PCDHGA12 and CDO1 DNA Methylation in Bronchial Washing Fluid for Lung Cancer Diagnosis

• Park SJ
• Kang D
• Lee M
• Lee SY
• Park YG
• Oh T
• Jang S
• Hwang WJ
• Kwon SJ
• An S
• Son JW
• Jeong IB

• KMID: 2550802
• DOI: http://doi.org/10.3346/jkms.2024.39.e28

Abstract

Background
When suspicious lesions are observed on computer-tomography (CT), invasive tests are needed to confirm lung cancer. Compared with other procedures, bronchoscopy has fewer complications. However, the sensitivity of peripheral lesion through bronchoscopy including washing cytology is low. A new test with higher sensitivity through bronchoscopy is needed. In our previous study, DNA methylation of PCDHGA12 in bronchial washing cytology has a diagnostic value for lung cancer. In this study, combination of PCDHGA12 and CDO1 methylation obtained through bronchial washing cytology was evaluated as a diagnostic tool for lung cancer.
Methods
A total of 187 patients who had suspicious lesions in CT were enrolled. PCDHGA12 methylation test, CDO1 methylation test, and cytological examination were performed using 3-plex LTE-qMSP test.
Results
Sixty-two patients were diagnosed with benign diseases and 125 patients were diagnosed with lung cancer. The sensitivity of PCDHGA12 was 74.4% and the specificity of PCDHGA12 was 91.9% respectively. CDO1 methylation test had a sensitivity of 57.6% and a specificity of 96.8%. The combination of both PCDHGA12 methylation test and CDO1 methylation test showed a sensitivity of 77.6% and a specificity of 90.3%. The sensitivity of lung cancer diagnosis was increased by combining both PCDHGA12 and CDO1 methylation tests.
Conclusion
Checking DNA methylation of both PCDHGA12 and CDO1 genes using bronchial washing fluid can reduce the invasive procedure to diagnose lung cancer.

Keyword

Lung Cancer; DNA Methylation; PCDHGA12; CDO1; Bronchial Washing Fluid

Figure

• 

  Fig. 1 Flowchart of the combined analysis of protocadherin gamma subfamily A12 and cysteine dioxygenase type 1 DNA methylation for lung cancer.LTE-qMSP = Linear Target Enrichment-quantitative methylation specific real-time polymerase chain reaction, LC = lung cancer.aExcluded due to insufficient specimen quantity; bexcluded due to unclear diagnosis or metastatic cancer.

• 

  Fig. 2 The DNA methylation level of PCDHGA12 gene (A) and CDO1 (B) in lung cancer patients and non-LC patients. PCDHGA12 = protocadherin gamma subfamily A12, CDO1 = cysteine dioxygenase type 1, LC = lung cancer.

• 

  Fig. 3 Receiver operating characteristic curve for PCDHGA12 gene (A) and CDO1 (B) for diagnosing lung cancer in bronchial washing fluids. PCDHGA12 = protocadherin gamma subfamily A12, CDO1 = cysteine dioxygenase type 1, AUC = area under receiver operating characteristic.

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