Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, P.R. China.
Department of Urology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, China.
Bioengineered. 2021 Dec;12(1):2649-2663. doi: 10.1080/21655979.2021.1937910.
In recent years, genes associated with N6-methyladenosine (m6A) modification were found to participate in modulation of multiple tumor biological processes. Concomitantly, the significantly complicated dual effects of tumor microenvironment have been observed on cancer progression. The present study aims to investigate m6A-related immune genes (m6AIGs) for their signatures and prognostic values in bladder cancer (BC). Out of 2856 differentially expressed genes (DEGs) of BC, a total of 85 genes were obtained following intersection of DEGs, immune genes and m6A-related genes. The results of multivariate Cox regression analysis illustrated four genes (BGN, GRK5, IL32, and SREBF1) were significantly associated with the prognosis of BC patients. The BC samples were divided into two types based on the consensus clustering, and the principal component analysis demonstrated a separation between them. It was found that high expression of BGN and GRK5 were linked with advanced T and N stage, and the expression of SREBF1 in early T stage was higher than that in advanced T stage. Subsequently, the nomogram to predict 3- and 5-year survival probability of BC patients was developed and calibrated. GSEA analysis for risk subgroups showed WNT and TGF-beta signaling pathways were involved in regulation of BC progression in high risk level group. In the low risk level group, cytosolic DNA-Sensing cGAS-STING and RIG-I-like receptors signaling pathways were found to be correlated with BC development. These findings provide a novel insight on studies for BC progression.
近年来,研究发现与 N6-甲基腺苷(m6A)修饰相关的基因参与调节多种肿瘤生物学过程。同时,肿瘤微环境的复杂双重作用对癌症进展的影响也受到了关注。本研究旨在探讨膀胱癌(BC)中 m6A 相关免疫基因(m6AIGs)的特征和预后价值。在 2856 个 BC 的差异表达基因(DEGs)中,通过 DEGs、免疫基因和 m6A 相关基因的交集,共获得了 85 个基因。多变量 Cox 回归分析的结果表明,有 4 个基因(BGN、GRK5、IL32 和 SREBF1)与 BC 患者的预后显著相关。根据共识聚类将 BC 样本分为两种类型,主成分分析表明它们之间存在分离。结果发现,BGN 和 GRK5 的高表达与较晚的 T 和 N 分期有关,而 SREBF1 在早期 T 分期的表达高于晚期 T 分期。随后,开发并校准了用于预测 BC 患者 3 年和 5 年生存率的列线图。风险亚组的 GSEA 分析表明,WNT 和 TGF-β信号通路参与了高危水平组 BC 进展的调控。在低危水平组中,发现细胞质 DNA 感应 cGAS-STING 和 RIG-I 样受体信号通路与 BC 的发生相关。这些发现为 BC 进展的研究提供了新的视角。