TET1 methylation and mRNA expression in renal cell carcinoma: implications for tumor staging and prognosis.

BACKGROUND: Renal cell carcinoma (RCC) is a prevalent cancer characterized by intricate molecular mechanisms that contribute to its advancement. Epigenetic alterations, particularly DNA methylation, play a critical role in cancer development. This research examines TET1 gene methylation's involvement in RCC development and its viability as a diagnostic marker. METHODS: We evaluated TET1 expression in 532 RCC tumor samples and 72 adjacent normal tissues using data from the TCGA database. A clinical case-control study involving 40 RCC patients and matched controls was conducted to evaluate TET1 methylation at nine CpG sites in the promoter region using pyrosequencing. The relationship between TET1 methylation, clinical indicators, and tumor markers was evaluated by combining clinical samples and cell experiments. The diagnostic efficacy of TET1 methylation and mRNA expression levels were assessed using ROC curve analysis. RESULTS: TET1 expression was notably reduced in RCC tumor tissues relative to adjacent normal tissues (P < 0.05) and was elevated in early stage (T1 and stage 1) tumors compared to advanced stages. RCC patients exhibited significantly higher methylation levels at all nine CpG sites and in the mean methylation level compared to controls (P < 0.001). Gender-specific analysis revealed lower TET1 methylation levels in males compared to females, with significant differences at CpG1-CpG8 sites (P < 0.05). TET1 methylation levels were positively correlated with tumor stage, tumor size, and serum markers, such as CA125, NSE and Ki67 (P < 0.05), and significantly negatively correlated with TET1 expression (r = - 0.665, P < 0.001). ROC curve analysis showed that the combination of TET1 average methylation and mRNA expression level (AUC = 0.876) had a high diagnostic efficacy. The levels of TET1 and p21 in RCC patients and 786-O cells were significantly reduced, and the level of Ki67 was significantly increased, suggesting that TET1 methylation may participate in the mechanism of malignant proliferation of RCC tumor cells by regulating p21 and Ki67. CONCLUSIONS: This study underscores the importance of TET1 methylation in RCC progression and its promise as an early stage diagnostic biomarker, and may be involved in the mechanism of malignant proliferation of RCC cells. These findings offer fresh perspectives on RCC's epigenetic regulation and highlight TET1's potential in therapy and diagnosis.