DNA methylation of metallothionein genes is associated with the clinical features of renal cell carcinoma

  • Authors:
    • Ruta Maleckaite
    • Algirdas Zalimas
    • Arnas Bakavicius
    • Feliksas Jankevicius
    • Sonata Jarmalaite
    • Kristina Daniunaite
  • View Affiliations

  • Published online on: April 10, 2019     https://doi.org/10.3892/or.2019.7109
  • Pages: 3535-3544
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Abstract

Metallothioneins are low‑weight cysteine‑rich proteins responsible for metal ion homeostasis in a cell and, thus, capable of regulating cell proliferation and differentiation. Deregulation of metallothionein genes has been reported in various human tumors. However, their role in renal cell carcinoma (RCC) has been poorly investigated. In the present study, we aimed to evaluate the importance of promoter DNA methylation of selected metallothionein genes for RCC. Based on the initial analysis of kidney renal clear cell carcinoma dataset from The Cancer Genome Atlas, genes MT1E, MT1F, MT1G and MT1M were selected for qualitative methylation analysis in 30 tumors (including 10 multifocal cases), 10 pericancerous, and 30 non‑cancerous renal tissues (NRT). Methylation of MT1E and MT1M was tumor‑specific (P=0.0056 and P=0.0486, respectively) and showed moderate interfocal variation in paired tumor foci. Methylated promoter status of the two genes was associated with larger tumor size (P=0.0110 and P=0.0156, respectively). Furthermore, aberrant MT1E methylation was more frequent in tumors having necrotic zones (P=0.0449) or characterized with higher differentiation grade (P=0.0144), while MT1M was more commonly methylated in tumors with higher Fuhrman grade (P=0.0272). Only unmethylated MT1F promoter status was observed in all analyzed samples. Gene expression analysis (51 RCC and 9 NRT) revealed MT1G downregulation in tumors (P<0.0001), while lower MT1E expression levels were associated with the promoter methylation (P=0.0077). In clear cell RCC, MT1E, MT1G and MT1M expression was higher than that noted in other histological tumor subtypes (all P<0.0500). In addition, some associations were observed between metabolic syndrome‑related clinical parameters and promoter methylation or gene expression. In conclusion, the present study revealed the potential role of MT1E and MT1M promoter methylation in RCC development.

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June 2019
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Copy and paste a formatted citation
APA
Maleckaite, R., Zalimas, A., Bakavicius, A., Jankevicius, F., Jarmalaite, S., & Daniunaite, K. (2019). DNA methylation of metallothionein genes is associated with the clinical features of renal cell carcinoma. Oncology Reports, 41, 3535-3544. https://doi.org/10.3892/or.2019.7109
MLA
Maleckaite, R., Zalimas, A., Bakavicius, A., Jankevicius, F., Jarmalaite, S., Daniunaite, K."DNA methylation of metallothionein genes is associated with the clinical features of renal cell carcinoma". Oncology Reports 41.6 (2019): 3535-3544.
Chicago
Maleckaite, R., Zalimas, A., Bakavicius, A., Jankevicius, F., Jarmalaite, S., Daniunaite, K."DNA methylation of metallothionein genes is associated with the clinical features of renal cell carcinoma". Oncology Reports 41, no. 6 (2019): 3535-3544. https://doi.org/10.3892/or.2019.7109