Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer

Cancers

Loretta De Chiara¹  Diana Valverde¹  Mar Rodríguez-Girondo²  Virginia Leiro³  Manuel Núñez-Delgado³  Alberto Fernández-Villar³  Maribel Botana-Rial³ 

[1] Department of Biochemistry, Genetics and Immunology, Biomedical Research Center (CINBIO), University of Vigo, 36310 Vigo, Spain;Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands;Pulmonary Department, Hospital Álvaro Cunqueiro, Vigo Health Area, 36312 Vigo, Spain;

关键词: DNA methylation;    mediastinal and hilar lymph node;    staging;    diagnosis;    lung cancer;    biomarker;    endobronchial ultrasound;    bronchoscopy;   

DOI  :  10.3390/cancers11101408

来源: DOAJ

【 摘 要 】

The evaluation of mediastinal lymph nodes is critical for the correct staging of patients with lung cancer (LC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for mediastinal staging, though unfortunately lymph node micrometastasis is often missed by cytological analysis. The aim of this study was to evaluate the predictive capacity of methylation biomarkers and provide a classification rule for predicting malignancy in false negative EBUS-TBNA samples. The study included 112 patients with a new or suspected diagnosis of LC that were referred to EBUS-TBNA. Methylation of p16/INK4a, MGMT, SHOX2, E-cadherin, DLEC1, and RASSF1A was quantified by nested methylation-specific qPCR in 218 EBUS-TBNA lymph node samples. Cross-validated linear regression models were evaluated to predict malignancy. According to EBUS-TBNA and final diagnosis, 90 samples were true positives for malignancy, 110 were true negatives, and 18 were false negatives. MGMT, SHOX2, and E-cadherin were the methylation markers that better predicted malignancy. The model including sex, age, short axis diameter and standard uptake value of adenopathy, and SHOX2 showed 82.7% cross-validated sensitivity and 82.4% specificity for the detection of malignant lymphadenopathies among negative cytology samples. Our results suggest that the predictive model approach proposed can complement EBUS-TBNA for mediastinal staging.

【 授权许可】

Unknown