Department of General Surgery, The First People's Hospital of Yulin, Yulin, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
BMC Cancer. 2023 Nov 17;23(1):1122. doi: 10.1186/s12885-023-11550-6.
Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated.
The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism.
The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS.
Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC.
越来越多的证据表明，Ⅱ型胱抑素（CST）基因在多种肿瘤病理过程中发挥着关键作用，从而影响肿瘤发生和发展的所有阶段。然而，Ⅱ型 CST 基因在 GC 中的预后和预测价值尚未得到研究。
本研究通过使用癌症基因组图谱（TCGA）数据库和 Kaplan-Meier 绘图仪（KM plotter）在线数据库评估了Ⅱ型 CST 基因在 GC 中的表达和预后价值。然后筛选出与 GC 预后相关的Ⅱ型 CST 基因。我们通过免疫组织化学验证了这些基因的表达和预后价值。我们还使用数据库注释、可视化和综合发现（DAVID）、基因多重关联网络集成算法（GeneMANIA）、搜索工具检索相互作用基因/蛋白（STRING）、列线图、全基因组共表达分析和其他生物信息学工具来分析Ⅱ型 CST 基因在 GC 中的价值和潜在机制。
TCGA 数据库和 KM plotter 在线数据库的数据显示，CST2 和 CST4 的高表达与 GC 患者的总生存期（OS）相关。免疫组织化学表达分析显示，GC 组织中 CST4 高表达的患者 OS 短于 CST4 低表达的患者（HR=1.85，95%CI：1.13-3.03，P=0.015）。多因素 Cox 回归分析证实 CST4 高表达是 OS 的独立预后危险因素。
我们的研究结果表明，CST4 可以作为影响 GC 预后的肿瘤标志物，并可作为 GC 的潜在治疗靶点。
