前列腺癌中 m5C 甲基化调控基因与肿瘤微环境的综合分析

BACKGROUND: 5-Methylcytidine (m5C) methylation is an emerging epigenetic modification in recent years, which is associated with the development and progression of various cancers. However, the prognostic value of m5C regulatory genes and the correlation between m5C methylation and the tumor microenvironment (TME) in prostate cancer remain unknown. METHODS: In the current study, the genetic and transcriptional alterations and prognostic value of m5C regulatory genes were investigated in The Cancer Genome Atlas and Gene Expression Omnibus datasets. Then, an m5C prognostic model was established by LASSO Cox regression analysis. Gene set variation analyses (GSVA), gene set enrichment analysis (GSEA), clinical relevance, and TME analyses were conducted to explain the biological functions and quantify the TME scores between high-risk and low-risk subgroups. m5C regulatory gene clusters and m5C immune subtypes were identified using consensus unsupervised clustering analysis. The Cell-type Identification By Estimating Relative Subsets of RNA Transcripts algorithm was used to calculate the contents of immune cells. RESULTS: was upregulated at transcriptional levels in PCa compared with normal tissues, and a high expression was associated with poor prognosis. An m5C prognostic model consisting of 3 genes (, , and ) was developed and a nomogram was constructed for improving the clinical applicability of the model. Functional analysis revealed the enrichment of pathways and the biological processes associated with RNA regulation and immune function. Significant differences were also found in the expression levels of m5C regulatory genes, TME scores, and immune cell infiltration levels between different risk subgroups. We identified two distinct m5C gene clusters and found their correlation with patient prognosis and immune cell infiltration characteristics. Naive B cells, CD8+ T cells, M1 macrophages and M2 macrophages were obtained and 2 m5C immune subtypes were identified. , , , and were differentially expressed between immune subtypes. The expression of was found to be correlated with the degree of immune cell infiltration. CONCLUSIONS: Our comprehensive analysis of m5C regulatory genes in PCa demonstrated their potential roles in the prognosis, clinical features, and TME. These findings may improve our understanding of m5C regulatory genes in the tumor biology of PCa.

背景：5-甲基胞嘧啶（m5C）甲基化是近年来新兴的一种表观遗传修饰，与多种癌症的发生和发展有关。然而，m5C 调节基因的预后价值以及 m5C 甲基化与前列腺癌肿瘤微环境（TME）之间的相关性尚不清楚。

方法：在本研究中，我们在 The Cancer Genome Atlas 和 Gene Expression Omnibus 数据集上研究了 m5C 调节基因的遗传和转录改变以及预后价值。然后，通过 LASSO Cox 回归分析建立了 m5C 预后模型。进行了基因集变异分析（GSVA）、基因集富集分析（GSEA）、临床相关性和 TME 分析，以解释高风险和低风险亚组之间的生物学功能和量化 TME 评分。使用共识无监督聚类分析确定 m5C 调节基因簇和 m5C 免疫亚型。使用 Cell-type Identification By Estimating Relative Subsets of RNA Transcripts 算法计算免疫细胞的含量。

结果：与正常组织相比，m5C 在 PCa 中呈转录水平上调，高表达与预后不良相关。构建了一个包含 3 个基因（、和）的 m5C 预后模型，并构建了一个列线图以提高模型的临床适用性。功能分析揭示了与 RNA 调节和免疫功能相关的途径和生物学过程的富集。在不同风险亚组之间，m5C 调节基因的表达水平、TME 评分和免疫细胞浸润水平也存在显著差异。我们确定了两个不同的 m5C 基因簇，并发现它们与患者预后和免疫细胞浸润特征相关。获得了幼稚 B 细胞、CD8+T 细胞、M1 巨噬细胞和 M2 巨噬细胞，并鉴定出 2 个 m5C 免疫亚型。在免疫亚型之间差异表达了、、和。发现的表达与免疫细胞浸润程度相关。

结论：我们对 PCa 中 m5C 调节基因的综合分析表明，它们在预后、临床特征和 TME 中具有潜在作用。这些发现可能有助于我们更好地理解 m5C 调节基因在前列腺癌肿瘤生物学中的作用。