Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Medical Oncology, Department of Cancer Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Hum Genomics. 2024 Jul 9;18(1):77. doi: 10.1186/s40246-024-00631-7.
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.
大多数具有 E3 泛素连接酶的 TRIM 家族成员参与泛素化和肿瘤发生。虽然在胃癌 (GC) 中对整个家族进行全面研究的情况很少。通过结合 TCGA 和 GEO 数据库，获得了常见的 TRIM 家族成员 (TRIMs)，以研究基因表达、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免疫组织化学分析。合并数据集包含 66 个 TRIMs，其中 52 个差异表达，43 个差异预后。共识聚类分析获得的基因簇之间存在显著的生存差异。使用多变量 Cox 回归和 LASSO 回归鉴定的 4 个差异表达基因，建立了风险评分系统。较高的风险评分与预后不良、抑制性免疫细胞浸润和耐药性有关。转录组数据和临床样本组织微阵列证实 TRIM31 在 GC 中高表达，并与预后不良相关。通路富集分析、细胞迁移和集落形成试验、EdU 试验、活性氧 (ROS) 试验和线粒体膜电位试验表明，TRIM31 可能参与细胞周期调节和氧化应激相关通路，有助于胃癌的发生。本研究调查了 TRIM 家族在 GC 中的全功能和表达谱以及风险评分系统。围绕 TRIM31 的进一步研究提供了深入了解其家族其他成员在 GC 背景下作用机制的见解。
