Gene selection driven by DNA methylation in relation to lymph node metastasis in prostate cancer and prognosis analysis

Abstract

Abstract Purpose Lymph node metastasis is an independent prognostic factor for prostate cancer (PCa), and this study aims to explore the intrinsic molecular mechanisms of PCa lymph node metastasis based on epigenetic modifications using bioinformatics.Methods Gene expression data set TCGA PRAD was downloaded from the UCSC Xena database for differential analysis. Differential genes between patients with and without lymph node metastasis were identified and functionally annotated. DNA methylation data from the GSE220910 dataset were used to identify differential methylation sites (DMPs) using the "ChAMP" R package. The correlation between differential gene expression values and methylation probe beta values was calculated and tested for significance. Finally, a prognosis analysis was conducted for the selected genes regulated by DNA methylation.Results We identified 1380 significantly differentially expressed genes (DEGs), including 906 upregulated and 474 downregulated genes. GO analysis revealed that upregulated genes in patients with lymph node metastasis were mainly involved in processes such as cell division and mitosis, while downregulated genes participated in the cellular response to copper and zinc ions. Subsequently, we further selected 81009 differential methylation sites (DMPs), ultimately retaining 263 DEGs associated with 382 DMPs. Correlation analysis showed that LTA, DOK3, TNFRSF25, and CHRM1 had Pearson correlation coefficients of -0.4092, -0.4111, -0.4054, and − 0.4598, respectively (P < 0.05), with their corresponding methylation probes. Survival analysis indicated that high expression of LTA, DOK3, and TNFRSF25 genes was associated with a shortened progression-free interval (PFI) in PCa patients, while CHRM1 showed the opposite trend (P < 0.05).Conclusion Lymph node metastasis in PCa patients is associated with active cell division and suppression of the response to metal ions. We also discovered that LTA, DOK3, TNFRSF25, and CHRM1 are regulated by DNA methylation, and their abnormal expression significantly impacts patient prognosis.