Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer
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...
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MDPI AG
2019-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/10/1408 |
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| author | Virginia Leiro Loretta De Chiara Mar Rodríguez-Girondo Maribel Botana-Rial Diana Valverde Manuel Núñez-Delgado Alberto Fernández-Villar |
| author_facet | Virginia Leiro Loretta De Chiara Mar Rodríguez-Girondo Maribel Botana-Rial Diana Valverde Manuel Núñez-Delgado Alberto Fernández-Villar |
| author_sort | Virginia Leiro |
| collection | DOAJ |
| description | 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 <i>p16/INK4a</i>, <i>MGMT</i>, <i>SHOX2</i>, <i>E-cadherin</i>, <i>DLEC1</i>, and <i>RASSF1A</i> 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. <i>MGMT</i>, <i>SHOX2</i>, and <i>E-cadherin</i> were the methylation markers that better predicted malignancy. The model including sex, age, short axis diameter and standard uptake value of adenopathy, and <i>SHOX2</i> 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. |
| first_indexed | 2024-03-12T06:15:07Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:15:07Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c6e4a4cb0ea94797b07e666b1a608f492023-09-03T02:41:23ZengMDPI AGCancers2072-66942019-09-011110140810.3390/cancers11101408cancers11101408Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung CancerVirginia Leiro0Loretta De Chiara1Mar Rodríguez-Girondo2Maribel Botana-Rial3Diana Valverde4Manuel Núñez-Delgado5Alberto Fernández-Villar6Pulmonary Department, Hospital Álvaro Cunqueiro, Vigo Health Area, 36312 Vigo, SpainDepartment of Biochemistry, Genetics and Immunology, Biomedical Research Center (CINBIO), University of Vigo, 36310 Vigo, SpainDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, The NetherlandsPulmonary Department, Hospital Álvaro Cunqueiro, Vigo Health Area, 36312 Vigo, SpainDepartment of Biochemistry, Genetics and Immunology, Biomedical Research Center (CINBIO), University of Vigo, 36310 Vigo, SpainPulmonary Department, Hospital Álvaro Cunqueiro, Vigo Health Area, 36312 Vigo, SpainPulmonary Department, Hospital Álvaro Cunqueiro, Vigo Health Area, 36312 Vigo, SpainThe 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 <i>p16/INK4a</i>, <i>MGMT</i>, <i>SHOX2</i>, <i>E-cadherin</i>, <i>DLEC1</i>, and <i>RASSF1A</i> 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. <i>MGMT</i>, <i>SHOX2</i>, and <i>E-cadherin</i> were the methylation markers that better predicted malignancy. The model including sex, age, short axis diameter and standard uptake value of adenopathy, and <i>SHOX2</i> 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.https://www.mdpi.com/2072-6694/11/10/1408DNA methylationmediastinal and hilar lymph nodestagingdiagnosislung cancerbiomarkerendobronchial ultrasoundbronchoscopy |
| spellingShingle | Virginia Leiro Loretta De Chiara Mar Rodríguez-Girondo Maribel Botana-Rial Diana Valverde Manuel Núñez-Delgado Alberto Fernández-Villar Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer Cancers DNA methylation mediastinal and hilar lymph node staging diagnosis lung cancer biomarker endobronchial ultrasound bronchoscopy |
| title | Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer |
| title_full | Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer |
| title_fullStr | Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer |
| title_full_unstemmed | Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer |
| title_short | Methylation Assessment for the Prediction of Malignancy in Mediastinal Adenopathies Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Patients with Lung Cancer |
| title_sort | methylation assessment for the prediction of malignancy in mediastinal adenopathies obtained by endobronchial ultrasound guided transbronchial needle aspiration in patients with lung cancer |
| topic | DNA methylation mediastinal and hilar lymph node staging diagnosis lung cancer biomarker endobronchial ultrasound bronchoscopy |
| url | https://www.mdpi.com/2072-6694/11/10/1408 |
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