Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung 802213, Taiwan.
Division of Family Medicine, Department of Community Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung 802213, Taiwan.
Biomolecules. 2022 May 6;12(5):670. doi: 10.3390/biom12050670.
Gastric cancer (GC) is one of the leading malignant diseases worldwide, especially in Asia. CAST is a potential oncogene in GC carcinogenesis. The character of macrophage infiltration in the GC microenvironment also remains unaddressed.
We first applied machine searching to evaluate gene candidates for GC. CAST expression and pan-cancer surveyance were analyzed using the Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. The protein-protein interaction (PPI) network was downloaded from STRING. We investigated the impact of CAST on clinical prognosis using a Kaplan-Meier plotter. The correlations between CAST and Lgr5 and macrophage infiltration in GC were determined using TIMER 2.0. Finally, GeneMANIA was also used to evaluate the possible functional linkages between genes.
After the machine-assisted search, CAST expression was found to significantly influence the overall survival of GC patients. STRING revealed CAST-related proteomic and transcriptomic associations, mainly concerning the CAPN family. Moreover, CAST significantly impacts the prognosis of GC based on the validation of other datasets. Notably, high CAST expression was correlated with worse overall survival in GC patients (hazard ratio = 1.59; log-rank P = 9.4 × 10). CAST and Lgr5 expression were both positively correlated with WNT 2 and WNT 2B. Among the GC patients in several datasets, CAST and macrophage infiltration, evaluated together, showed no obvious association with poor clinical overall survival.
CAST plays an important role in the clinical prognosis of GC and is associated with WNT 2/WNT 2B/Lgr5. Our study demonstrates that CAST's influence on overall survival in GC is regulated by macrophage infiltration.
胃癌（GC）是全球主要的恶性疾病之一，尤其在亚洲。CAST 是 GC 发生过程中的一个潜在癌基因。GC 微环境中巨噬细胞浸润的特征也尚未得到解决。
我们首先应用机器搜索来评估 GC 的候选基因。使用人类蛋白质图谱（HPA）和基因表达谱交互式分析 2（GEPIA2）数据库分析 CAST 的表达和泛癌调查。从 STRING 下载蛋白质-蛋白质相互作用（PPI）网络。我们使用 Kaplan-Meier 绘图器研究 CAST 对临床预后的影响。使用 TIMER 2.0 确定 CAST 与 GC 中 Lgr5 和巨噬细胞浸润的相关性。最后，还使用 GeneMANIA 评估基因之间可能的功能联系。
经过机器辅助搜索，发现 CAST 表达显著影响 GC 患者的总生存率。STRING 揭示了 CAST 相关的蛋白质组学和转录组学关联，主要涉及 CAPN 家族。此外，基于对其他数据集的验证，CAST 显著影响 GC 的预后。值得注意的是，CAST 高表达与 GC 患者总体生存率较差相关（危险比=1.59；对数秩检验 P=9.4×10）。CAST 和 Lgr5 表达均与 WNT 2 和 WNT 2B 呈正相关。在几个数据集的 GC 患者中，CAST 和巨噬细胞浸润一起评估，与不良临床总生存率没有明显关联。
CAST 在 GC 的临床预后中起重要作用，并与 WNT 2/WNT 2B/Lgr5 相关。我们的研究表明，CAST 对 GC 总生存率的影响受巨噬细胞浸润的调节。
