脂蛋白脂酶（LPL）是脂质代谢中至关重要的基因，对恶性肿瘤的进展有显著作用。本研究的目的是研究发现于LPL基因3'UTR区域的rs15285对胃癌（GC）风险、生物学行为和预后的影响以及其潜在功能。通过SNaPshot技术对888例GC患者和874个对照进行了rs15285的基因分型。我们使用生物信息学分析和体外实验研究rs15285的作用。首先，本研究首次揭示了多态性rs15285增加GC风险（OR = 1.48，95%CI = 1.16-1.89，P = 0.002）。虽然没有发现rs12585与GC的病理特征之间的关系，但rs12585 TT基因型个体的预后比CC或CC+CT基因型的患者差（HR = TT vs. CC为2.39，P = 0.025；HR = TT vs. CC+CT为2.38，P = 0.025）。此外，生物信息学分析显示rs12585可能影响miRNA与LPL的结合，导致LPL expression增加以促进癌症进展。最终，体外实验表明，rs15285 T等位基因在mRNA和蛋白质水平上增加LPL expression，促进GC细胞的增殖、侵袭和转移。 LPL rs12528 TT基因型增加了GC的风险并预测了不良预后。机制上，rs15285 T等位基因可以提高LPL的表达，从而促进GC的恶性表型。因此，我们的研究可能为胃癌患者的预后和个体化治疗提供新的生物学预测因子和理论基础。要点：• Rs15285多态性是GC的风险因素。• Rs12585 TT基因型预测GC个体的不良预后。• Rs15285 T等位基因增强GC细胞的恶性生物学行为。 © 2023. 作者，独家许可 Springer-Verlag GmbH Germany 发布，属于 Springer Nature 的部分。

Lipoprotein lipase (LPL), a crucial gene in lipid metabolism, has a significant role in the progression of malignant tumors. The purpose of this research was to investigate the impact of rs15285 found in the LPL gene's 3'UTR region on the risk, biological behavior, and gastric cancer (GC) prognosis as well as to examine its potential function. Genotyping of rs15285 in 888 GC cases and 874 controls was conducted by SNaPshot technology. We used bioinformatics analysis and in vitro experiments to study the role of rs15285. First, this study revealed for the first time that polymorphism rs15285 increases the risk of GC (OR = 1.48, 95%CI = 1.16-1.89, P = 0.002). Although no relationship was found between rs12585 and the pathological features of GC, the prognosis of individuals with the rs12585 TT genotype was poorer than that of patients with the CC or CC+CT genotype (HR = 2.39 for TT vs. CC, P = 0.025; HR = 2.38 for TT vs. CC+CT, P = 0.025). In addition, bioinformatics analysis showed rs12585 may affect the binding of miRNAs to LPL, resulting in an increase of LPL expression to promote cancer progression. Ultimately, in vitro tests revealed that the rs15285 T allele increased LPL expression on the mRNA as well as the protein levels, promoting GC cell proliferation, invasion, and metastasis. The LPL rs12528 TT genotype increased the risk of GC and predicted a poor prognosis. Mechanistically, the rs15285 T allele could improve the expression of LPL, and thus promotes the malignant phenotype of GC. Therefore, our study may provide new biological predictors and a theoretical basis for the prognosis and customized therapy of stomach cancer patients. KEY POINTS: • Rs15285 polymorphism is a risk factor for GC. • Rs12585 TT genotype predicts a bad outcome in GC individuals. • Rs15285 T allele enhances GC cells malignant biological behavior.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.