NALCN Promoter Methylation as a Biomarker for Metastatic Risk in a Cohort of Non-Small Cell Lung Cancer Patients
- 1Analysis of Circulating Tumor Cells, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, 15771 Athens, Greece.
- 2Department of Medical Oncology, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
- 3Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis-Zografou, 15771 Athens, Greece.
- 48th Department of Pulmonary Diseases, "Sotiria" General Hospital, 11527 Athens, Greece.
- 5First Department of Medical Oncology, Metropolitan General Hospital, 15562 Athens, Greece.
- 6Department of Medical Oncology, University General Hospital of Larissa, 41334 Larissa, Greece.
- 0Analysis of Circulating Tumor Cells, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, 15771 Athens, Greece.
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View abstract on PubMed
Summary
This summary is machine-generated.Epigenetic silencing of NALCN, a tumor suppressor, via promoter hypermethylation is linked to worse outcomes in non-small cell lung cancer (NSCLC). This NALCN methylation in circulating tumor DNA (ctDNA) may predict metastasis.
Area Of Science
- Oncology
- Molecular Biology
- Epigenetics
Background
- Liquid biopsy analyzes circulating tumor DNA (ctDNA) and cells (CTCs) for real-time cancer monitoring.
- NALCN, a sodium leak channel, functions as a tumor suppressor and is implicated in cancer progression and immunity.
- NALCN deletion correlates with increased metastasis and CTCs in peripheral blood.
Purpose Of The Study
- To investigate NALCN promoter methylation in non-small cell lung cancer (NSCLC) cell lines, tissues, and ctDNA.
- To assess the relationship between NALCN methylation, expression, and clinical outcomes in NSCLC patients.
- To evaluate NALCN methylation in ctDNA as a potential biomarker for metastasis.
Main Methods
- Real-time methylation-specific PCR (MSP) was developed and used to analyze NALCN promoter methylation.
- NALCN expression was quantified via mRNA levels in NSCLC tissues.
- NALCN methylation was assessed in Aza-treated cell lines, paired NSCLC tissues, and ctDNA from NSCLC patients and healthy donors.
Main Results
- NALCN was underexpressed in 54.5% of NSCLC tumor tissues, with higher expression in recurrence-free patients.
- NALCN promoter hypermethylation was associated with worse disease-free intervals (DFIs) in NSCLC patients.
- NALCN methylation was detected in ctDNA from 5.1% of early-stage and 10.2% of advanced NSCLC cases.
Conclusions
- Epigenetic inactivation of NALCN through promoter hypermethylation may predict metastasis in NSCLC.
- NALCN promoter methylation in ctDNA shows potential as a prognostic biomarker for NSCLC.
- Further validation in larger cohorts is needed to confirm NALCN methylation as a biomarker for metastasis and prognosis.
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