DNPEP与ALDH18A1在胃癌中的表达特征及其对细胞增殖、迁移与侵袭的影响

Expression Characteristics of DNPEP and ALDH18A1 in Gastric Cancer and Their Effects on Cell Proliferation, Migration and Invasion

摘要: 目的：观察DNPEP及ALDH18A1在胃癌组织中的表达差异，分析其对胃癌细胞增殖、迁移与侵袭能力的影响。方法：借助TCGA数据库分析DNPEP、ALDH18A1在胃癌与癌旁组织的表达差异及基因表达和患者预后的关联性。运用RT-qPCR检测基因在胃癌细胞系的基础表达，筛选实验细胞株。经脂质体转染构建基因敲低、过表达细胞模型，结合CCK-8、划痕愈合、Transwell实验，探究基因对胃癌细胞增殖、迁移及侵袭能力的影响。结果：数据库分析显示，胃癌组织中DNPEP、ALDH18A1表达显著上调，高表达与患者预后改善相关。MKN-1细胞株在两种基因的表达呈中等水平(P < 0.001)，选定为细胞模型。RT-qPCR技术筛选可高效沉默的靶基因(P < 0.001)。功能实验揭示，过表达任一基因均能显著增强细胞活性、侵袭与迁移能力(均P < 0.001)；敲低后则导致细胞增殖(P < 0.001)、侵袭(P < 0.001, P < 0.01)及迁移能力(P < 0.001, P < 0.01)明显受阻。结论：DNPEP、ALDH18A1在胃癌中呈高表达，体外实验证实其具备促癌作用，但其高表达却对应更佳预后，存在体内外功能差异。二者作用机制复杂，有望作为胃癌诊断标志物与治疗靶点，仍需体内实验进一步验证。

Abstract: Objective: To observe the differential expression of DNPEP and ALDH18A1 in gastric cancer tissues and analyze their effects on the proliferation, migration, and invasion abilities of gastric cancer cells. Methods: The TCGA database was used to analyze the expression differences of DNPEP and ALDH18A1 between gastric cancer and adjacent normal tissues, as well as the correlation between gene expression and patient prognosis. RT-qPCR was performed to detect the basal expression of these genes in gastric cancer cell lines to screen for suitable experimental cell lines. Liposome transfection was used to construct gene knockdown and overexpression cell models. CCK-8, wound healing, and Transwell assays were employed to evaluate the effects of these genes on the proliferation, migration, and invasion abilities of gastric cancer cells. Results: Database analysis showed that the expression of DNPEP and ALDH18A1 was significantly upregulated in gastric cancer tissues, and high expression was associated with improved patient prognosis. The MKN-1 cell line exhibited moderate expression levels of both genes (P < 0.001) and was selected as the cell model. RT-qPCR confirmed that siRNA could efficiently silence the target genes (P < 0.001). Functional assays revealed that overexpression of either gene significantly enhanced cell proliferation, invasion, and migration (all P < 0.001), whereas knockdown significantly inhibited cell proliferation (P < 0.001), invasion (P < 0.001, P < 0.01), and migration (P < 0.001, P < 0.01). Conclusions: DNPEP and ALDH18A1 are highly expressed in gastric cancer, and in vitro experiments confirmed their oncogenic roles; however, their high expression is associated with better prognosis, indicating a discrepancy between in vitro and in vivo functions. Their mechanisms of action are complex, and they hold promise as diagnostic biomarkers and therapeutic targets for gastric cancer, though further validation through in vivo experiments is required.