A panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer

Abstract Lung cancer remains the leading cause of cancer deaths worldwide. Although low-dose spiral computed tomography (LDCT) screening is used for the detection of lung cancer in a high-risk population, false-positive results of LDCT remain a clinical problem. Here, we developed a blood test of a...

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Autores principales: Bing Wei, Fengxin Wu, Wenqun Xing, Haibo Sun, Chi Yan, Chengzhi Zhao, Dongqing Wang, Xiaobing Chen, Yanli Chen, Mingming Li, Jie Ma
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/8541ccf271504b21b2b6ac9441c1c0c9
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spelling oai:doaj.org-article:8541ccf271504b21b2b6ac9441c1c0c92021-12-02T16:45:41ZA panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer10.1038/s41598-021-96242-62045-2322https://doaj.org/article/8541ccf271504b21b2b6ac9441c1c0c92021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96242-6https://doaj.org/toc/2045-2322Abstract Lung cancer remains the leading cause of cancer deaths worldwide. Although low-dose spiral computed tomography (LDCT) screening is used for the detection of lung cancer in a high-risk population, false-positive results of LDCT remain a clinical problem. Here, we developed a blood test of a novel panel of three established lung cancer methylation biomarkers for lung cancer detection. Short stature homeobox 2 gene (SHOX2), ras association domain family 1A gene (RASSF1A), and prostaglandin E receptor 4 gene (PTGER4) methylation was analyzed in a training cohort of 351 individuals (197 controls, 154 cases) and validated from an independent cohort of 149 subjects (89 controls, 60 cases). The novel panel biomarkers distinguished between malignant and benign lung disease at high sensitivity and specificity: 87.0% sensitivity [95% CI 80.2–91.5%], 98.0% specificity [95% CI 94.9–99.4%]. Sensitivity in adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and other lung cancer was 89.0%, 87.5%, 85.7%, and 77.8%, respectively. Notably, cancer patients in stage I and II showed high diagnostic sensitivity at 82.5% and 90.5%, respectively. Moreover, the diagnostic efficiency did not show bias toward age, gender, smoking, and the presence of other (nonlung) cancers. The performance of the panel in the validation cohort confirmed the diagnostic value. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer.Bing WeiFengxin WuWenqun XingHaibo SunChi YanChengzhi ZhaoDongqing WangXiaobing ChenYanli ChenMingming LiJie MaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Bing Wei
Fengxin Wu
Wenqun Xing
Haibo Sun
Chi Yan
Chengzhi Zhao
Dongqing Wang
Xiaobing Chen
Yanli Chen
Mingming Li
Jie Ma
A panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer
description Abstract Lung cancer remains the leading cause of cancer deaths worldwide. Although low-dose spiral computed tomography (LDCT) screening is used for the detection of lung cancer in a high-risk population, false-positive results of LDCT remain a clinical problem. Here, we developed a blood test of a novel panel of three established lung cancer methylation biomarkers for lung cancer detection. Short stature homeobox 2 gene (SHOX2), ras association domain family 1A gene (RASSF1A), and prostaglandin E receptor 4 gene (PTGER4) methylation was analyzed in a training cohort of 351 individuals (197 controls, 154 cases) and validated from an independent cohort of 149 subjects (89 controls, 60 cases). The novel panel biomarkers distinguished between malignant and benign lung disease at high sensitivity and specificity: 87.0% sensitivity [95% CI 80.2–91.5%], 98.0% specificity [95% CI 94.9–99.4%]. Sensitivity in adenocarcinoma, squamous cell carcinoma, small cell lung cancer, and other lung cancer was 89.0%, 87.5%, 85.7%, and 77.8%, respectively. Notably, cancer patients in stage I and II showed high diagnostic sensitivity at 82.5% and 90.5%, respectively. Moreover, the diagnostic efficiency did not show bias toward age, gender, smoking, and the presence of other (nonlung) cancers. The performance of the panel in the validation cohort confirmed the diagnostic value. These findings clearly showed that this panel of DNA methylation biomarkers was effective in detecting lung cancer noninvasively and may provide clinical utility in stand-alone or in combination with current imaging techniques to improve the diagnosis of lung cancer.
format article
author Bing Wei
Fengxin Wu
Wenqun Xing
Haibo Sun
Chi Yan
Chengzhi Zhao
Dongqing Wang
Xiaobing Chen
Yanli Chen
Mingming Li
Jie Ma
author_facet Bing Wei
Fengxin Wu
Wenqun Xing
Haibo Sun
Chi Yan
Chengzhi Zhao
Dongqing Wang
Xiaobing Chen
Yanli Chen
Mingming Li
Jie Ma
author_sort Bing Wei
title A panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer
title_short A panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer
title_full A panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer
title_fullStr A panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer
title_full_unstemmed A panel of DNA methylation biomarkers for detection and improving diagnostic efficiency of lung cancer
title_sort panel of dna methylation biomarkers for detection and improving diagnostic efficiency of lung cancer
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/8541ccf271504b21b2b6ac9441c1c0c9
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