PDF(Pubmed)
Abstract：
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality in the world. However, identifying key genes that can be exploited for the effective diagnosis and management of HCC remains difficult. The study aims to examine the prognostic and diagnostic value of TRIM28-H2AX-CDK4 axis in HCC. Analysis in TCGA, GSEA and Gene expression profiling interactive analysis online tools were performed to explore the expression profiles of TRIM28, H2AX and CDK4. Data demonstrating the correlation between TRIM28 expression levels and immune infiltration states or the expression of genes associated with immune checkpoints genes were exacted from TCGA and TIMER. Genetic alteration and enrichment analysis were performed using the cBioPortal and GEPIA2 tools. Finally, the expression of these proteins in HCC was then examined and validated in an independent cohort using immunohistochemistry. TRIM28 alteration exhibited co-occurrence instead of mutual exclusivity with a large number of immune checkpoint components and tumor-infiltrating immune cells, especially B cells, were found to serve roles in patients with HCC with different TRIM28 expression levels. Higher expression levels of TRIM28, H2AX and CDK4 were associated with a poorer prognosis and recurrence in patients with HCC according to TCGA, which was validated further in an independent cohort of patients with HCC. Area under curve revealed the superior predictive power of applying this three-gene signatures in this validation cohort. The diagnostic model based on this TRIM28-H2AX-CDK4 signature is efficient and provides a novel strategy for the clinical management of HCC.
摘要：
肝细胞癌（HCC）是世界上癌症相关死亡率的第二大原因。然而,确定可用于有效诊断和治疗HCC的关键基因仍然很困难。该研究旨在检查TRIM28-H2AX-CDK4轴在HCC中的预后和诊断价值。TCGA中的分析，进行GSEA和基因表达谱分析交互式在线分析工具以探索TRIM28、H2AX和CDK4的表达谱。来自TCGA和TIMER的数据表明TRIM28表达水平与免疫浸润状态或与免疫检查点基因相关的基因表达之间的相关性。使用cBioPortal和GEPIA2工具进行遗传改变和富集分析。最后,然后使用免疫组织化学在独立队列中检查并验证了这些蛋白质在HCC中的表达。TRIM28改变与大量免疫检查点成分和肿瘤浸润性免疫细胞共同发生，而不是相互排斥。尤其是B细胞,发现在具有不同TRIM28表达水平的HCC患者中发挥作用。根据TCGA，较高的TRIM28，H2AX和CDK4的表达水平与HCC患者预后较差和复发相关。这在一个独立的HCC患者队列中得到了进一步的验证。曲线下面积揭示了在该验证队列中应用该三基因签名的优越预测能力。基于此TRIM28-H2AX-CDK4特征的诊断模型是有效的，并为HCC的临床管理提供了新的策略。
