ArticleCancer science2023
Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma.
Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Schistosoma haematobium infection is associated with oncogenic gene expression in Cervical Mucosa, with enhanced effects following treatment: A pilot study.PLoS neglected tropical diseases · 2025Article
- Plasma cell-free DNA methylation profile before afatinib treatment is associated with progression-free and overall survival of patients with epidermal growth factor receptor gene mutation-positive non-small cell lung cancer.Clinical epigenetics · 2025Article
- Micropapillary structure: A natural tumor collective invasion model with enhanced stem-like properties.Cancer science · 2025Review
- Research Progress of Liquid Biopsy Based on DNA Methylation in Tumor Diagnosis and Treatment.Biomolecules · 2024Review
- Methylation-related differentially expressed genes as potential prognostic biomarkers for cervical cancer.Heliyon · 2024Article
- Epigenetic characterization of housekeeping core promoters and their importance in tumor suppression.Nucleic acids research · 2024Article
- Article
- Impact of lung adenocarcinoma subtypes on survival and timing of brain metastases.Frontiers in oncology · 2024Article
- Association of frequent hypermethylation with high grade histological subtype in lung adenocarcinoma.Cancer science · 2023Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
Lung adenocarcinoma is classified morphologically into five histological subtypes according to the WHO classification. While each histological subtype correlates with a distinct prognosis, the molecular basis has not been fully elucidated. Here we conducted DNA methylation analysis of 30 lung adenocarcinoma cases annotated with the predominant histological subtypes and three normal lung cases using the Infinium BeadChip. Unsupervised hierarchical clustering analysis revealed three subgroups with different methylation levels: high-, intermediate-, and low-methylation epigenotypes (HME, IME, and LME). Micropapillary pattern (MPP)-predominant cases and those with MPP components were significantly enriched in HME (p = 0.02 and p = 0.03, respectively). HME cases showed a significantly poor prognosis for recurrence-free survival (p < 0.001) and overall survival (p = 0.006). We identified 365 HME marker genes specifically hypermethylated in HME cases with enrichment of "cell morphogenesis" related genes; 305 IME marker genes hypermethylated in HME and IME, but not in LME, with enrichment "embryonic organ morphogenesis"-related genes; 257 Common marker genes hypermethylated commonly in all cancer cases, with enrichment of "regionalization"-related genes. We extracted surrogate markers for each epigenotype and designed pyrosequencing primers for five HME markers (TCERG1L, CXCL12, FAM181B, HOXA11, GAD2), three IME markers (TBX18, ZNF154, NWD2) and three Common markers (SCT, GJD2, BARHL2). DNA methylation profiling using Infinium data was validated by pyrosequencing, and HME cases defined by pyrosequencing results also showed the worse recurrence-free survival. In conclusion, lung adenocarcinomas are stratified into subtypes with distinct DNA methylation levels, and the high-methylation subtype correlated with MPP-predominant cases and those with MPP components and showed a poor prognosis.
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