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Aberrant DNA Methylation of NPTX2 as an Indicator of Malignant Behavior in Thymic Epithelial Tumors
Kazuya Kondo1, Kyoka Muguruma1, Shiho Soejima1
1Department of Oncological Medical Services, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8509, Japan.
Abstract:
Thymic epithelial tumors (TET) consist of thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT). Genetic and epigenetic alterations in TET have been the focus of recent research. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in TET, and this identified neuronal pentraxin 2 (NTPX2) as a significantly hypermethylated CpG island in TC relative to thymomas. NPTX2 is released from pre-synaptic cells in response to neuronal activity/seizure, and plays a role in host immunity and acute inflammation. TET samples were obtained from 38 thymomas, 25 TC, and 6 NECTT. The DNA methylation, mRNA, and protein expression levels of NPTX2 were examined. The DNA methylation rate of the NPTX2 gene was significantly higher in TC than in the normal thymus and thymomas, except B3. The mRNA expression level of NPTX2 was lower in TC than in the normal thymus. An inverse relationship was observed between mRNA expression levels and methylation levels. Relapse-free survival was shorter in patients with high NPTX2 DNA methylation levels than in those with low DNA methylation levels. NECTT showed very high mRNA and protein expression levels and low DNA methylation levels of NPTX2. NPTX2 may function as a tumor suppressor in TC, and have an oncogenic function in NECTT.
Insights
Neuronal pentraxin 2 (NPTX2) is hypermethylated in thymic carcinoma (TC), correlating with poorer survival. NPTX2 may act as a tumor suppressor in TC but oncogenic in neuroendocrine tumors of the thymus.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Thymic epithelial tumors (TET) encompass thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT).
- Recent research focuses on genetic and epigenetic alterations in TET.
- Neuronal pentraxin 2 (NPTX2) is involved in neuronal activity, immunity, and inflammation.
Purpose of the Study:
- To investigate the role of aberrantly methylated CpG islands in TET.
- To identify specific methylation patterns associated with different TET subtypes.
- To examine the expression and function of NPTX2 in TET.
Main Methods:
- Genome-wide screening for aberrantly methylated CpG islands in TET.
- Analysis of DNA methylation, mRNA, and protein expression of NPTX2 in TET samples (38 thymomas, 25 TC, 6 NECTT).
- Correlation analysis between NPTX2 methylation/expression and clinical outcomes (relapse-free survival).
Main Results:
- NPTX2 was significantly hypermethylated in TC compared to thymomas.
- NPTX2 mRNA expression was lower in TC, inversely correlating with methylation levels.
- High NPTX2 DNA methylation was associated with shorter relapse-free survival in TC patients.
- NECTT exhibited high NPTX2 mRNA/protein expression and low DNA methylation.
Conclusions:
- NPTX2 methylation patterns differ across TET subtypes.
- NPTX2 may function as a tumor suppressor in thymic carcinoma.
- NPTX2 might have an oncogenic role in neuroendocrine tumors of the thymus.
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