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Identification of diagnostic DNA methylation biomarkers specific for early-stage lung adenocarcinoma

  • Qidong Cai
    Affiliations
    Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

    Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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  • Pengfei Zhang
    Affiliations
    Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

    Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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  • Boxue He
    Affiliations
    Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

    Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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  • Zhenyu Zhao
    Affiliations
    Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

    Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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  • Yuqian Zhang
    Affiliations
    Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

    Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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  • Xiong Peng
    Affiliations
    Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

    Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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  • Hui Xie
    Affiliations
    Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

    Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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  • Xiang Wang
    Correspondence
    Corresponding author.
    Affiliations
    Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China

    Hunan Key Laboratory of Early Diagnosis and Precision Therapy, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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      Highlights

      • 160 genes were aberrantly methylated in LUAD since stage I.
      • We evaluated LUAD-specific methylation diagnostic biomarkers and established a diagnostic model with superior sensitivity and specificity.
      • This model could distinguish between LUAD and LUSC.
      • The HOXA1 gene showed higher methylation levels in LUAD than in 10 other cancers.
      • HOXA1 may be a LUAD-specific diagnostic biomarker.

      Abstract

      Background

      DNA hypermethylation is a key event in oncogenesis and may act as a biomarker for the early detection of lung adenocarcinoma (LUAD). Here, we aimed to identify LUAD-specific methylation diagnostic biomarkers and explored potential mechanisms using data mining.

      Methods

      Using The Cancer Genome Atlas (TCGA) LUAD and GSE83842 datasets, we identified overlapping common differentially methylated positions (DMPs) with negative correlations between methylation and gene expression. Methylation profiles of the TCGA LUAD samples were compared with 185 blood samples and 370 lung squamous cell carcinoma (LUSC) samples to build a logistic regression model. Diagnosis performance was evaluated using an independent dataset.

      Results

      160 genes were aberrantly methylated in LUAD since stage I; these genes were enriched in DNA-binding transcription factor activity, multiple embryonic development processes, and cell signaling. A diagnostic prediction model based on 10 CpG could distinguish LUAD from LUSC (area under the curve: 0.943). The derived model showed higher sensitivity and specificity than the two existing models. The homeobox A1 gene exhibited significantly higher methylation levels in LUAD than in 10 other cancers, showing potential as a LUAD-specific diagnostic biomarker.

      Conclusions

      Our findings provided insights into DNA methylation alterations in LUAD and established LUAD-specific diagnostic biomarkers.

      Keywords

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