目的:利用生物信息学和细胞实验探讨鞘氨醇激酶2（sphingosine kinase 2，SPHK2）在胃癌（gastric cancer，GC）中的表达及其与预后的联系，并评估其潜在诊疗价值。 方法:通过HPA、GEPIA数据库分析SPHK2在GC中的表达，并检验其与MKI67（Ki‑67）表达的相关性；利用Kaplan‑Meier Plotter数据库评估SPHK2表达与GC患者预后的关系；借助UCSC和TIMER2.0数据库探讨SPHK2与肿瘤微环境的联系；基于Sangerbox数据库研究SPHK2表达与免疫治疗的关联；使用cBioPortal、Metascape数据库分析SPHK2基因突变及富集情况；采用免疫组织化学染色技术检测SPHK2表达与GC患者临床病理特征之间的关联性；在HGC‑27细胞系中利用慢病毒敲低SPHK2，使用Western blot检测各蛋白表达，结合CCK‑8、克隆形成实验探讨细胞增殖，并通过细胞划痕和Transwell小室实验评估细胞的迁移能力。 结果:SPHK2在GC组织中明显上调（P<0.05），与MKI67表达成正相关（r=0.21，P=1.1×10^-5）；生存分析显示，GC中SPHK2高表达与较差的总生存期（P=0.00 024）和进展后生存期（P=1.1×10^-6）相关；TIMER2.0和Sangerbox数据库分析表明SPHK2表达与B细胞、CD4⁺T细胞相关（P<0.05），并可作为评估免疫检查点抑制剂在GC患者中治疗成效的指标；GO和KEGG富集分析显示SPHK2可能参与多条GC发生相关的通路；细胞实验表明，对照组（SPHK2‑nc）的增殖和迁移能力优于实验组（SPHK2‑sh），说明SPHK2对GC细胞的增殖与迁移有明显影响（P<0.05）。 结论:SPHK2在GC患者中呈现高表达，影响细胞增殖与迁移能力，并与肿瘤微环境及免疫检查点基因密切相关，可以作为评估GC诊断、预后及免疫治疗效果的潜在指标。

Objective:To investigate the expression of sphingosine kinase 2 （SPHK2） in gastric cancer （GC） and its relationship with prognosis by bioinformatics and cell experiments， and to evaluate its potential diagnostic and therapeutic value. Methods:The expression of SPHK2 in GC was analyzed by HPA and GEPIA databases， and its correlation with MKI67 （Ki‑67） expression was tested. Kaplan‑Meier Plotter database was used to evaluate the relationship between SPHK2 expression and prognosis of GC patients. The relationship between SPHK2 and tumor microenvironment was explored by UCSC and TIMER2.0 database. The association of SPHK2 expression with immunotherapy was studied based on the Sangerbox database. The cBioPortal and Metascape databases were used to analyze the mutation and enrichment of SPHK2 gene. Immunohistochemical staining （IHC） was used to detect the correlation between SPHK2 expression and clinicopathological features of GC patients. SPHK2 was knocked down by lentivirus in HGC‑27 cell line. Western blot was used to detect the expression of each protein. CCK‑8 and clone formation experiments were used to investigate cell proliferation. Cell scratch and Transwell chamber experiments were used to evaluate cell migration. Results:The expression of SPHK2 was significantly up‑regulated in GC tissues （P<0.05）， which was positively correlated with the expression of MKI67 （r=0.21，P=1.1×10^-5）. Survival analysis showed that high expression of SPHK2 in GC was associated with poor overall survival （P=0.000 24） and post‑progressive survival （P=1.1×10^-6）. TIMER2.0 and Sangerbox database analysis showed that SPHK2 expression was associated with B cells and CD4⁺ T cells （P<0.05）， and could be used as an indicator to evaluate the efficacy of immune checkpoint inhibitors in patients with GC. GO and KEGG enrichment analysis showed that SPHK2 may be involved in multiple GC‑related pathways. Cell experiments showed that the proliferation and migration of the control group （SPHK2‑nc） were better than those of the experimental group （SPHK2‑sh）， indicating that SPHK2 had a significant effect on the proliferation and migration of GC cells （P<0.05）. Conclusions:SPHK2 is highly expressed in GC patients， affects cell proliferation and migration， and is closely related to tumor microenvironment and immune checkpoint genes. It can be used as a potential index to evaluate the diagnosis， prognosis and immunotherapy effect of GC.

R735.2;Q811.4

安徽省高等学校自然科学研究项目（KJ2021ZD0090）；蚌埠医学院研究生科研创新项目（Byycx22090）；安徽省2023年度新时代育人省级质量工程项目（2023xscx125）