PDF(Pubmed)
Abstract：
Most TRIM family members characterized by the E3-ubiquitin ligases, participate in ubiquitination and tumorigenesis. While there is a dearth of a comprehensive investigation for the entire family in gastric cancer (GC). By combining the TCGA and GEO databases, common TRIM family members (TRIMs) were obtained to investigate gene expression, gene mutations, and clinical prognosis. On the basis of TRIMs, a consensus clustering analysis was conducted, and a risk assessment system and prognostic model were developed. Particularly, TRIM31 with clinical prognostic and diagnostic value was chosen for single-gene bioinformatics analysis, in vitro experimental validation, and immunohistochemical analysis of clinical tissue microarrays. The combined dataset consisted of 66 TRIMs, of which 52 were differentially expressed and 43 were differentially prognostic. Significant survival differences existed between the gene clusters obtained by consensus clustering analysis. Using 4 differentially expressed genes identified by multivariate Cox regression and LASSO regression, a risk scoring system was developed. Higher risk scores were associated with a poorer prognosis, suppressive immune cell infiltration, and drug resistance. Transcriptomic data and clinical sample tissue microarrays confirmed that TRIM31 was highly expressed in GC and associated with a poor prognosis. Pathway enrichment analysis, cell migration and colony formation assay, EdU assay, reactive oxygen species (ROS) assay, and mitochondrial membrane potential assay revealed that TRIM31 may be implicated in cell cycle regulation and oxidative stress-related pathways, contribute to gastric carcinogenesis. This study investigated the whole functional and expression profile and a risk score system based on the TRIM family in GC. Further investigation centered around TRIM31 offers insight into the underlying mechanisms of action exhibited by other members of its family in the context of GC.
摘要：
大多数TRIM家族成员以E3-泛素连接酶为特征，参与泛素化和肿瘤发生。尽管缺乏对整个家庭进行胃癌（GC）的全面调查。通过结合TCGA和GEO数据库，获得常见的TRIM家族成员(TRIMs)来研究基因表达，基因突变,和临床预后。在TRIMs的基础上，进行了共识聚类分析，并建立了风险评估系统和预后模型。特别是,选择具有临床预后和诊断价值的TRIM31进行单基因生物信息学分析，体外实验验证，和临床组织微阵列的免疫组织化学分析。合并的数据集由66个TRIM组成，其中52个差异表达，43个差异预后。通过共识聚类分析获得的基因簇之间存在显着的生存差异。使用通过多变量Cox回归和LASSO回归鉴定的4个差异表达基因，开发了风险评分系统。较高的风险评分与较差的预后相关，抑制免疫细胞浸润，和抗药性。转录组数据和临床样本组织微阵列证实，TRIM31在GC中高表达，并与不良预后相关。途径富集分析，细胞迁移和集落形成试验，EdU分析，活性氧（ROS）测定，和线粒体膜电位分析显示，TRIM31可能参与细胞周期调控和氧化应激相关途径，有助于胃癌的发生。这项研究调查了GC中基于TRIM家族的整个功能和表达谱以及风险评分系统。围绕TRIM31进行的进一步调查可深入了解其家族其他成员在GC背景下表现出的潜在作用机制。
