Whole-genome DNA methylation and DNA methylation-based biomarkers in lung squamous cell carcinoma
Qidong Cai,
Boxue He,
Guangxu Tu,
Weilin Peng,
Shuai Shi,
Banglun Qian,
Qingchun Liang,
Shaoliang Peng,
Yongguang Tao,
Xiang Wang
Affiliations
Qidong Cai
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital, Central South University, Changsha 410011, China
Boxue He
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital, Central South University, Changsha 410011, China
Guangxu Tu
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital, Central South University, Changsha 410011, China
Weilin Peng
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital, Central South University, Changsha 410011, China
Shuai Shi
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital, Central South University, Changsha 410011, China
Banglun Qian
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital, Central South University, Changsha 410011, China
Qingchun Liang
Department of Pathology, Second Xiangya Hospital, Central South University, Changsha 410011, China
Shaoliang Peng
College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China; School of Computer Science, National University of Defense Technology, Changsha 410073, China; Peng Cheng Lab, Shenzhen 518000, China
Yongguang Tao
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital, Central South University, Changsha 410011, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Hunan 410078, China; NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan 410078, China
Xiang Wang
Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China; Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Second Xiangya Hospital, Central South University, Changsha 410011, China; Corresponding author
Summary: Exploring early detection methods through comprehensive evaluation of DNA methylation for lung squamous cell carcinoma (LUSC) patients is of great significance. By using different machine learning algorithms for feature selection and model construction based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, five methylation biomarkers in LUSC (along with mapped genes) were identified including cg14823851 (TBX4), cg02772121 (TRIM15), cg10424681 (C6orf201), cg12910906 (ARHGEF4), and cg20181079 (OR4D11), achieving extremely high sensitivity and specificity in distinguishing LUSC from normal samples in independent cohorts. Pyrosequencing assay verified DNA methylation levels, meanwhile qRT-PCR and immunohistochemistry results presented their accordant methylation-related gene expression statuses in paired LUSC and normal lung tissues. The five methylation-based biomarkers proposed in this study have great potential for the diagnosis of LUSC and could guide studies in methylation-regulated tumor development and progression.
