Department of Urology, Third Xiangya Hospital, Central South University, Changsha, China.
Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2023 Mar 23;14:1086907. doi: 10.3389/fimmu.2023.1086907. eCollection 2023.
Despite the recent progress of therapeutic strategies in treating prostate cancer (PCa), the majority of patients still eventually relapse, experiencing dismal outcomes. Therefore, it is of utmost importance to identify novel viable targets to increase the effectiveness of treatment. The present study aimed to investigate the potential relationship between N6-methyladenosine (m6A) RNA modification and PCa development and determine its clinical relevance.
Through systematic analysis of the TCGA database and other datasets, we analyzed the gene expression correlation and mutation profiles of m6A-related genes between PCa and normal tissues. Patient samples were divided into high- and low-risk groups based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis. Subsequently, differences in biological processes and genomic characteristics of the two risk groups were determined, followed by functional enrichment analysis and gene set enrichment (GSEA) analysis. Next, we constructed the protein-protein interaction (PPI) network of differentially expressed genes between patients in high- and low-risk groups, along with the mRNA-miRNA-lncRNA network. The correlation analysis of tumor-infiltrating immune cells was further conducted to reveal the differences in immune characteristics between the two groups.
A variety of m6A-related genes were identified to be differentially expressed in PCa tissues as compared with normal tissues. In addition, the PPI network contained 278 interaction relationships and 34 m6A-related genes, and the mRNA-miRNA-lncRNA network contained 17 relationships, including 91 miRNAs. Finally, the immune characteristics analysis showed that compared with the low-risk group, the levels of M1 and M2 macrophages in the high-risk group significantly increased, while the levels of mast cells resting and T cells CD4 memory resting significantly decreased.
This study provides novel findings that can further the understanding of the role of m6A methylation during the progression of PCa, which may facilitate the invention of targeted therapeutic drugs.
尽管在治疗前列腺癌（PCa）的治疗策略方面取得了最近的进展，但大多数患者最终仍会复发，预后较差。因此，识别新的可行靶标以提高治疗效果至关重要。本研究旨在探讨 N6-甲基腺苷（m6A）RNA 修饰与 PCa 发展之间的潜在关系，并确定其临床相关性。
通过系统分析 TCGA 数据库和其他数据集，我们分析了 m6A 相关基因在 PCa 和正常组织中的基因表达相关性和突变谱。根据最小绝对收缩和选择算子（LASSO）Cox 分析的结果，将患者样本分为高风险组和低风险组。随后，确定两组之间的生物学过程和基因组特征差异，然后进行功能富集分析和基因集富集（GSEA）分析。接下来，我们构建了高风险组和低风险组患者之间差异表达基因的蛋白质-蛋白质相互作用（PPI）网络，以及 mRNA-miRNA-lncRNA 网络。进一步进行肿瘤浸润免疫细胞的相关性分析，以揭示两组之间免疫特征的差异。
鉴定出多种 m6A 相关基因在 PCa 组织中与正常组织相比存在差异表达。此外，PPI 网络包含 278 个相互作用关系和 34 个 m6A 相关基因，mRNA-miRNA-lncRNA 网络包含 17 个关系，包括 91 个 miRNA。最后，免疫特征分析表明，与低风险组相比，高风险组中 M1 和 M2 巨噬细胞的水平显著增加，而静止肥大细胞和静止 T 细胞 CD4 记忆的水平显著降低。
本研究提供了新的发现，可以进一步了解 m6A 甲基化在 PCa 进展过程中的作用，这可能有助于发明靶向治疗药物。
