IRGM在肾透明细胞癌中的表达和预后价值及其与肿瘤增殖和迁移的关系

Expression and prognostic value of IRGM in clear cell renal cell carcinoma and its correlation with tumor proliferation and migration

摘要:

目的 探讨免疫相关GTP酶家族M（IRGM）在肾透明细胞癌（ccRCC）中的表达，并分析其与肿瘤增殖和迁移的关系。方法 使用癌症基因组图谱和基因表达综合数据库对IRGM的mRNA差异表达进行可视化分析。将ccRCC患者分为IRGM低表达组与IRGM高表达组，评估IRGM水平与临床病理特征的关系。使用Kaplan-Meier方法比较两组患者的存活率，采用Cox回归模型分析评估IRGM对ccRCC预后的影响，并构建预后列线图。此外，通过体外试验，包括实时荧光定量聚合酶链反应（qRT-PCR）和Western blotting实验检测IRGM基因和蛋白相对表达量，使用CCK-8法和平板克隆试验评估细胞的增殖能力，划痕试验和Transwell法评估细胞的迁移能力。结果 与邻近正常组织相比，ccRCC肿瘤组织中IRGM的表达升高（P < 0.05），IRGM与肿瘤分级、分期有关联（P < 0.05），与性别、年龄和N分期没有关联（P > 0.05）。IRGM高表达与ccRCC患者的总体生存期、疾病特异生存期和无进展间隔有关联（P < 0.05）。qRT-PCR和Western blotting结果表明，两种细胞系IRGM基因和蛋白相对表达量比较，差异均有统计学意义（P < 0.05）。敲低IRGM可抑制ccRCC细胞的克隆形成能力、增殖能力及迁移能力。结论 IRGM可能作为一种新的预后标志物，与ccRCC的肿瘤增殖和迁移能力密切相关，对于判断ccRCC的转移和预后具有重要的分子标记价值。

Abstract:

Objective To investigate the expression of Immunity-related GTPase family M (IRGM) in clear cell renal cell carcinoma (ccRCC) and analyze its correlation with tumor proliferation and migration.Methods Using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we performed visual analysis of IRGM mRNA differential expression. ccRCC patients were categorized into IRGM low- and high-expression groups to assess the correlation between IRGM levels and clinicopathological characteristics. The Kaplan-Meier method was used to compare survival rates, and COX regression analysis was conducted to evaluate the prognostic value of IRGM with construction of a prognostic nomogram. In vitro experiments included qRT-PCR and Western blotting for detecting IRGM expression, CCK-8 and colony formation assays for proliferation assessment, and scratch wound and Transwell assays for migration evaluation.Results Compared with adjacent normal tissues, IRGM expression was significantly elevated in ccRCC tissues (P < 0.05), showing significant correlations with tumor grade and stage (P < 0.05), but not with gender, age, or N stage (P > 0.05). High IRGM expression correlated with poorer overall survival, disease-specific survival, and progression-free interval (all P < 0.05). Both mRNA and protein expression levels showed statistically significant differences in two cell lines (P < 0.05). IRGM knockdown significantly inhibited colony formation, proliferation, and migration capacities of ccRCC cells.Conclusion IRGM may serve as a novel prognostic biomarker closely associated with tumor proliferation and migration in ccRCC, demonstrating significant molecular marker value for predicting metastasis and prognosis.