【摘要】 目的 研究血磷脂酰胆碱酰基转移酶1(LPCAT1)在肝细胞癌(HCC)中的表达水平、预后意义及潜在机制，重点探究LPCAT1与免疫细胞和免疫检查点的关系。方法 从肿瘤基因组图谱(TCGA)数据库获取HCC患者的临床信息及LPCAT1表达水平，利用回归分析和生存分析等探索LPCAT1与HCC患者的临床特征及预后的关系。通过功能富集分析进一步探索LPCAT1在HCC中的潜在机制。应用肿瘤免疫浸润评估资源(TIMER)数据库分析LPCAT1与免疫细胞浸润丰度和标志基因表达水平的相关性，应用cBioPortal数据库分析LPCAT1与HCC患者免疫检查点的遗传变异和表达水平的关系。通过细胞学实验验证LPCAT1在HCC中的表达水平，并通过敲减LPCAT1探究其对肝癌细胞恶性生物学行为的影响。结果 在HCC中，LPCAT1的表达水平升高，与较高的T分期(P=0.008)、组织学分级(P<0.001)、Edmondson-Steiner分级(P=0.002)、血清甲胎蛋白水平(P=0.019)以及发生血管侵袭(P<0.001)具有相关性，是HCC的独立风险因子和独立预后因子(P<0.001)。LPCAT1可能参与糖酵解、药物代谢、Wnt通路和MYC通路等多种病理生理过程和信号通路。敲减LPCAT1后肝癌细胞的体外增殖能力和迁移能力降低，差异有统计学意义(P<0.05)。LPCAT1与5种免疫抑制性细胞的浸润丰度及标志物的表达水平呈正相关，与免疫检查点的遗传变异和表达水平也具有一定的相关性。结论 LPCAT1在HCC中高表达，可作为独立风险因子和预后因子，可能通过影响免疫细胞浸润和免疫检查点参与免疫抑制性肿瘤微环境的构建，进而参与HCC进展。更多还原

【Abstract】 Objective To study the expression level of blood lysophosphatidylcholine acyltransferase 1(LPCAT1) in hepatocellular carcinoma(HCC), its prognostic significance and potential mechanism, especially the relationship between LPCAT1 and immune cell infiltration as well as immune checkpoints.Methods Clinicopathological information and LPCAT1 expression level of HCC were obtained from The Cancer Genome Atlas(TCGA) database. Regression analysis and survival analysis were used to explore the relationship between LPCAT1 and clinical characteristics and prognosis of HCC patients. Functional enrichment analysis was used to explore the potential mechanism of LPCAT1 in HCC. The Tumor Immune Estimation Resource(TIMER) database was applied to analyze the correlation between LPCAT1 and the abundance of immune cell infiltration and the expression level of marker genes. The cBioPortal database was applied to analyze the relationship between genetic variation and expression levels of LPCAT1 and immune checkpoints in HCC patients. The expression level of LPCAT1 in HCC was verified through cytological experiments, and its impact on the malignant biological behavior of liver cancer cells was explored by knocking down LPCAT1.Results In HCC, the expression level of LPCAT1 increased, which was correlated with higher T-stage(P=0.008), histologic grade(P<0.001), Edmondson-Steiner stage(P=0.002), serum alpha fetoprotein levels(P=0.019) and occurrence of vascular invasion(P<0.001), and was a potential independent risk factor and prognostic factor of HCC(P<0.001). LPCAT1 was possibly involved in various pathophysiological processes and signaling pathways such as glycolysis, drug metabolism, Wnt pathway and MYC pathway. After knocking down LPCAT1, the in vitro proliferation and migration ability of liver cancer cells were reduced, and the difference was statistically significant(P<0.05). LPCAT1 was positively correlated with the infiltration abundance and expression levels of five immunosuppressive cells, as well as with the genetic variation and expression levels of immune checkpoints.Conclusion LPCAT1 is highly expressed in HCC and can be used as an independent risk and prognostic factor, which may participate in the construction of immunosuppressive tumor microenvironment by affecting immune cell infiltration and immune checkpoints, and then participate in the progression of HCC.更多还原