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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Article Info
Publication History
Published online: August 06, 2020
Accepted:
August 3,
2020
Received in revised form:
July 30,
2020
Received:
May 1,
2020
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.
