College of Life Science, Shihezi University, Shihezi City, Xinjiang, China.
Sci Rep. 2024 Sep 6;14(1):20782. doi: 10.1038/s41598-024-71285-7.
Prostate cancer (PCa) is a highly heterogeneous disease, encompassing various molecular and clinical pathological subtypes. Fusion genes play a facilitating role in the occurrence and progression of PCa. We categorized PCa samples into the ETS family of transcription factors fusion positive and fusion negative subtypes based on fusion genes. This subtyping method is closely related to the epigenomic DNA methylation profiles of PCa, with each sample cluster including more than 85% of the patients. We conducted an analysis of the distribution of the ETS family fusion genes on chromosomes, fusion modes within reading frames, and predictions of structural domains. Among these, the highest frequency of the ETS family related fusion genes occurred on chromosome 21. Compared to the parental genes, fusion genes exhibited new structural domains, such as IG_like, and the most common fusion mode was out-of-frame fusion. The correlation between the methylation levels of hypermethylated CpG sites and the expression levels of their corresponding mRNAs indicates that CD8A and B3GNT5 (with correlations of - 0.388 and - 0.253, respectively) could serve as potential prognostic markers for PCa.
前列腺癌 (PCa) 是一种高度异质性疾病,包含各种分子和临床病理亚型。融合基因在 PCa 的发生和进展中起促进作用。我们根据融合基因将 PCa 样本分为 ETS 家族转录因子融合阳性和融合阴性亚型。这种分型方法与 PCa 的表观基因组 DNA 甲基化谱密切相关,每个样本聚类包含超过 85%的患者。我们对染色体上 ETS 家族融合基因的分布、阅读框内的融合模式以及结构域的预测进行了分析。其中,ETS 家族相关融合基因的最高频率发生在 21 号染色体上。与亲本基因相比,融合基因表现出新的结构域,如 IG_like,最常见的融合模式是框外融合。高甲基化 CpG 位点的甲基化水平与相应 mRNA 表达水平之间的相关性表明,CD8A 和 B3GNT5(相关系数分别为-0.388 和-0.253)可作为 PCa 的潜在预后标志物。