PCDHGA12 methylation biomarker in bronchial washing specimens as an adjunctive diagnostic tool to bronchoscopy in lung cancer

Abstract

The use of bronchoscopy is central to the diagnosis of lung cancer. However, the sensitivity of bronchoscopy is low. In addition, bronchial washing cytology, which is a routine adjunctive test, does not significantly improve the performance of bronchoscopy owing to its low sensitivity. To enhance the diagnostic performance of bronchoscopy, the protocadherin GA12 () methylation biomarker in bronchial washings was introduced as a novel adjunctive diagnostic test. A total of 98 patients who underwent bronchoscopy owing to suspicion of lung cancer were analyzed. Cytological examination and methylation biomarker testing of the bronchial washing fluid were performed. The performance of the tests was analyzed. The final diagnosis in 60 patients was lung cancer and in 38 patients was benign disease. The methylation biomarker had a sensitivity of 75.0%, a specificity of 78.9% and a positive predictive value (PPV) of 84.9%, whereas cytological assessment had a sensitivity of 45.0%, a specificity of 92.1% and a PPV of 90%. Patients with positive methylation test had an odds ratio for lung cancer of 11.25 (confidence interval, 4.25-29.8) compared with negative subjects. The combination of the two tests exhibited an increased sensitivity (83.3%), a specificity of 71.1% and a PPV of 82.0%. Furthermore, considering the non-diagnostic bronchoscopy group alone, the test demonstrated a sensitivity of 61.9% and a specificity of 78.9%. The results of the present study demonstrated that methylation, as a lung cancer biomarker in bronchial washings, may be a used as an adjunctive test to bronchoscopy.

DNA Methylation Cancer Biomarkers: Translation to the Clinic

“…Methylated SHOX2 and RASSF1A gene promoters were detected in lavage fluid from 322 patients with a sensitivity of 81% for lung cancer detection (Zhang et al, 2017). Other studies have also revealed high sensitivity for lung cancer detection using bronchoalveolar lavage fluid, with 75% and 78% for PCDHGA12 (Jeong et al, 2018) and SHOX2 (Dietrich et al, 2012) methylated DNA, respectively. However, these studies use different methodologies to process the lavage samples, so cannot be directly compared.…”

Quantitative analysis of a novel DNA hypermethylation panel using bronchial specimen for lung cancer diagnosis

“…In our study, the sensitivity of the panel in bronchial washing and brushing specimens was 74.8% and 86.5%, respectively, with specificity at 96.4% and 96.7%, respectively, which was higher than other methylation studies that used similar bronchial materials ranging from 74% to 95%. 10,25,29,30,39 While the sensitivity and specificity of brushing and washing are not higher than those achieved with bronchoscopy procedures incorporating cytology, ROSE technology and tissue histology, the NPV of the combination of bronchoscopy with q-MSP panel increases by 5.2% and 6.5% in bronchial washing and brushing sample groups, respectively. This increase may prevent further invasive procedures in some patients.…”

“…There have been few studies reported on the use of bronchoscopic brushing samples for diagnosing lung cancer 30,38,39 . However, the limited sample size or unsatisfactory performance of biomarkers in these studies make it difficult to draw definitive conclusions about the usefulness of brushing samples in diagnosis.…”

“…Non‐diagnostic bronchoscopy is a challenge in clinical practice, as it can lead to prolonged patient follow‐up and worsen the burden of the disease, particularly for malignant lesions that cannot be accurately diagnosed. Previous studies have used cytologically non‐diagnostic as the criterion for non‐diagnostic bronchoscopy, 18,31,39 which may not fully reflect current clinical practice. To address this issue, our study utilized a combination of cytology, ROSE and histology to identify non‐diagnostic cases and improve the accuracy of diagnosis, thereby reducing the incidence of non‐diagnostic bronchoscopy.…”

“…There have been few studies reported on the use of bronchoscopic brushing samples for diagnosing lung cancer. 30,38,39 However, the limited sample size or unsatisfactory performance of biomarkers in these studies make it difficult to draw definitive conclusions about the usefulness of brushing samples in diagnosis. Nevertheless, brushing samples have some advantages in the diagnostic process, such as containing sufficient DNA material for analysis even after being discarded after smearing on slides, and not changing current practice procedures.…”