胃癌（GC）是发生在消化系统中的最典型的恶性肿瘤之一。对于晚期GC患者来说，免疫治疗是延长生存时间的最后选择。因此，我们旨在确定增强GC个体免疫治疗反应的新的分子靶点。然后，我们应用生物信息学分析探索了G蛋白偶联受体27（GPR27）转录和GPR27甲基化的表达谱。随后分析了GC患者的存活与GPR27转录和甲基化的关联。我们还研究了GPR27表达与免疫细胞浸润水平之间的联系。最后，我们对97例GC个体的GPR27蛋白质的预测作用进行了深入研究。根据从TCGA获取的数据集，GC组织中的GPR27 mRNA表达较低。GPR27转录的下调与GC个体的较好存活相关，其中GPR27 cg03024619具有最显著的预测价值（HR = 0.553，P < 0.0001）。另外，GPR27的表达水平与免疫细胞浸润及其标记物之间存在明显的相互作用。单细胞分析显示，GPR27主要在巨噬细胞中表达。最后，我们观察到GC组织中的GPR27蛋白质下调与较好的生存结果相关。GPR27可以作为重要的预后生物标志物，在GC中发挥免疫调节作用。我们的研究结果强调了GPR27在包括GC在内的各种癌症中的重要性，并提供了从生物信息学和临床验证角度更好理解GPR27的线索。

Gastric cancer (GC) is one of the most typical cancerous neoplasms occurring in the digestive system. For advanced GC, immunotherapy is the final option for them to prolong survival time. Hence, we aimed to identify new molecular targets to enhance the immunotherapy response in GC individuals. Then we applied bioinformatic analysis to explore the expression profiles of G-protein-coupled receptor 27 (GPR27) transcription and GPR27 methylation. The associations between survival of GC patients and GPR27 transcription and methylation were then analyzed. We also studied the link between GPR27 expression and levels of immune cell infiltration. Finally, we gained insights into the prognostic role of GPR27 protein in 97 cases of GC individuals. According to datasets gained from TCGA, GPR27 mRNA is expressed lower in GC tissues. Down-regulation of GPR27 transcription was related with better survival in GC individuals, and GPR27 cg03024619 had the most significant prognostic value (HR=0.553, P<0.0001). In addition, the expression level of GPR27 has a clear interaction with immune cells' infiltration and their markers. Single-cell analysis displayed that GPR27 is mainly expressed in macrophages. Finally, down-regulation of GPR27 protein was observed in GC tissues and correlated with better survival outcomes. GPR27 can serve as an important prognostic biomarker and exert an immunomodulatory role in GC. Our findings highlight the significance of GPR27 in a variety of cancers, including GC, and provide clues for a better understanding of GPR27 from bioinformatics and clinically validated perspective.