ArticleMolecular brain2021
Integrated genomic and DNA methylation analysis of patients with advanced non-small cell lung cancer with brain metastases.
Article in Molecular brain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Advances in cerebrospinal fluid biomarkers for the diagnosis, treatment and monitoring of leptomeningeal metastases (Review).Oncology letters · 2026Review
- RNLS hypomethylation as a potential epigenetic marker of lung cancer metastasis: an epigenome-wide association study.British journal of cancer · 2026Article
- KDM3A drives NSCLC proliferation and metastasis via H3K9 demethylation, EMT activation and MMP-9 upregulation.Biomolecules & biomedicine · 2025Article
- Single-cell transcriptomic analyses provide insights into SPP1Cancer immunology, immunotherapy : CII · 2025Article
- Gut Microbes and Inflammation: Their Role in Spinal Cord Injury Progression and Secondary Damage.Current microbiology · 2025Review
- Nanopore-based cell-free DNA fragmentation and methylation profiles from the cerebral spinal fluid of patients with lung cancer brain metastases.bioRxiv : the preprint server for biology · 2025Article
- The epigenetic landscape of brain metastasis.Oncogene · 2025Review
- Identification and validation of a DNA methylation-block prognostic model in non-small cell lung cancer patients.BMC cancer · 2025Article
- Review
- A review on trends in development and translation of omics signatures in cancer.Computational and structural biotechnology journal · 2024Review
- Single-cell RNA sequencing reveals distinct transcriptomic profiles and evolutionary patterns in lung cancer brain metastasis.Heliyon · 2024Article
- Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States.The oncologist · 2023Article
- Prospects and feasibility of synergistic therapy with radiotherapy, immunotherapy, and DNA methyltransferase inhibitors in non-small cell lung cancer.Frontiers in immunology · 2023Review
- Genomic drivers of brain metastases in lung cancer.Neuro-oncology advancesReview
- Emerging blood-based biomarkers for the detection of parenchymal brain metastasis: Current progress and future perspectives.Neuro-oncology advancesReview
- Genomic landscape and actionable mutations of brain metastases derived from non-small cell lung cancer: A systematic review.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBrain metastasis is a common and lethal complication of non-small cell lung cancer (NSCLC). It is mostly diagnosed only after symptoms develop, at which point very few treatment options are available. Therefore, patients who have an increased risk of developing brain metastasis need to be identified early. Our study aimed to identify genomic and epigenomic biomarkers for predicting brain metastasis risk in NSCLC patients.
methodsPaired primary lung tumor tissues and either brain metastatic tissues or cerebrospinal fluid (CSF) samples were collected from 29 patients with treatment-naïve advanced NSCLC with central nervous system (CNS) metastases. A control group comprising 31 patients with advanced NSCLC who died without ever developing CNS metastasis was also included. Somatic mutations and DNA methylation levels were examined through capture-based targeted sequencing with a 520-gene panel and targeted bisulfite sequencing with an 80,672 CpG panel.
resultsCompared to primary lung lesions, brain metastatic tissues harbored numerous unique copy number variations. The tumor mutational burden was comparable between brain metastatic tissue (P = 0.168)/CSF (P = 0.445) and their paired primary lung tumor samples. Kelch-like ECH-associated protein (KEAP1) mutations were detected in primary lung tumor and brain metastatic tissue samples of patients with brain metastasis. KEAP1 mutation rate was significantly higher in patients with brain metastasis than those without (P = 0.031). DNA methylation analysis revealed 15 differentially methylated blocks between primary lung tumors of patients with and without CNS metastasis. A brain metastasis risk prediction model based on these 15 differentially methylated blocks had an area under the curve of 0.94, with 87.1% sensitivity and 82.8% specificity.
conclusionsOur analyses revealed 15 differentially methylated blocks in primary lung tumor tissues, which can differentiate patients with and without CNS metastasis. These differentially methylated blocks may serve as predictive biomarkers for the risk of developing CNS metastasis in NSCLC. Additional larger studies are needed to validate the predictive value of these markers.
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