Abstract
Non-small cell lung cancer (NSCLC) is the most prevalent histological type of lung cancer and the leading cause of death globally. Patients with NSCLC have a poor prognosis for various factors, and a late diagnosis is one of them. The DNA methylation of CpG island sequences found in the promoter regions of tumor suppressor genes has recently received attention as a potential biomarker of human cancer. In this study, we report DNA methylation changes of the adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1), which belongs to the ATP cassette transporter family in NSCLC patients. Our results demonstrate that ABCG1 is hyper-methylation in NSCLC samples, and these changes are negatively correlated to gene and protein expression. Furthermore, the expression of the ABCG1 gene is significantly associated with the survival time of lung adenocarcinoma (LUAD) patients; however, it did not show a correlation to overall survival (OS) of lung squamous cell carcinoma (LUSC) patients. Notably, we found ABCG1 methylation status at locus cg20214535 is strongly associated with the survival time and consistently observed hyper-methylation in LUAD samples. This novel finding suggests ABCG1 is a potential candidate for targeted therapy in lung cancer via this specific probe. In addition, we illustrate the protein–protein interaction (PPI) of ABCG1 with other proteins and the strong communication of ABCG1 with immune cells.
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Data availability
The datasets generated and/or analyzed during the current study are available in The Cancer Genome Atlas (TCGA) repository [https://portal.gdc.cancer.gov], projects TCGA-LUAD and TCGA-LUSC (accession date: 20 April 2022).
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Funding
This work is supported by the National Science and Technology Council, Taiwan [grant number MOST111-2628-E-038-002-MY3] and the Taiwan Higher Education Sprout Project by the Ministry of Education [grant number DP2-TMU-112-A-12].
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TOT: conceptualization, methodology, formal analysis, investigation, writing—original draft preparation. LHTL: conceptualization, visualization, writing—original draft preparation, writing—review and editing. NQKL: conceptualization, writing—review and editing, supervision, funding acquisition.
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ESM 1
Supplementary Figure S1. The number of DNA methylation samples available from TCGA project. LUAD: 458 tumor samples and 30 normal samples; LUSC: 364 tumor samples and 41 normal samples. Supplementary Figure S2. Analysis of ABCG1 protein level and its expression on cells/macrophages. (A) Analysis from ULCAN on CPTAC data set that includes 111 pairs of LUAD tissue. *: p $<$ 0.05; p-value of 0.04, data collected on 23 March 2023. (B) ABCG1 expression in lung alveolar cells and statistical analysis. (C) ABCG1 expression in lung macrophages and statistical analysis. Supplementary Table S1. GeneMANIA repot top 10 most gene-gene correlation of ABCG1. (PDF 763 kb)
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Tran, TO., Lam, L.H.T. & Le, N.Q.K. Hyper-methylation of ABCG1 as an epigenetics biomarker in non-small cell lung cancer. Funct Integr Genomics 23, 256 (2023). https://doi.org/10.1007/s10142-023-01185-y
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DOI: https://doi.org/10.1007/s10142-023-01185-y