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全面泛癌分析显示,LPCAT1 是一种新的预测预后和免疫治疗反应的生物标志物。

Comprehensive pancancer analysis reveals that LPCAT1 is a novel predictive biomarker for prognosis and immunotherapy response.

机构信息

Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Clinical Research Center For Breast Disease In Hunan Province, Changsha, Hunan, China.

出版信息

Apoptosis. 2024 Dec;29(11-12):2128-2146. doi: 10.1007/s10495-024-02010-y. Epub 2024 Aug 4.

Abstract

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a crucial enzyme involved in phospholipid metabolism and is essential for maintaining the structure and functionality of biofilms. However, a comprehensive examination of the role of LPCAT1 across various cancer types is lacking. Multiple public databases have been utilized to examine LPCAT1 expression, genetic alterations, methylation, prognosis, biological function, and its relationship with antitumor immunity in different cancer types. The function of LPCAT1 in glioma, breast cancer and liver cancer cells was further verified using in vitro experiments. Our research indicated that LPCAT1 is upregulated in various cancers and is accompanied by a wide range of amplification mutations. Higher LPCAT1 expression was associated with poorer prognosis across multiple cancers. Further in vitro experiments demonstrated that interfering with LPCAT1 expression increased apoptosis in glioma, breast cancer and liver cancer cells and concurrently suppressed their proliferation and migration. Functional enrichment analysis revealed that LPCAT1-associated genes were primarily enriched in immune and cancer progression pathways, such as the JAK/STAT, MYC, and EMT, etc. Moreover, LPCAT1 expression was closely associated with immune cell infiltration and immune checkpoint-related gene expression. Interestingly, LPCAT1 expression levels were generally higher in patients in the immunotherapy response group. The combination of LPCAT1 and PDL1 serves as an effective predictor of immunotherapy response. In conclusion, LPCAT1 is involved in immune regulation and tumor progression and holds promise as a biomarker for predicting patient outcomes and immunotherapy efficacy.

摘要

溶血磷脂酰胆碱酰基转移酶 1(LPCAT1)是一种参与磷脂代谢的关键酶,对于维持生物膜的结构和功能至关重要。然而,目前缺乏对 LPCAT1 在各种癌症类型中的作用的全面研究。本研究利用多个公共数据库,综合分析了 LPCAT1 在不同癌症类型中的表达、遗传改变、甲基化、预后、生物学功能及其与抗肿瘤免疫的关系。通过体外实验进一步验证了 LPCAT1 在神经胶质瘤、乳腺癌和肝癌细胞中的功能。研究结果表明,LPCAT1 在多种癌症中上调,并伴有广泛的扩增突变。在多种癌症中,LPCAT1 表达水平越高,患者预后越差。进一步的体外实验表明,干扰 LPCAT1 的表达可促进神经胶质瘤、乳腺癌和肝癌细胞的凋亡,同时抑制其增殖和迁移。功能富集分析表明,LPCAT1 相关基因主要富集在免疫和癌症进展相关通路,如 JAK/STAT、MYC 和 EMT 等。此外,LPCAT1 表达与免疫细胞浸润和免疫检查点相关基因表达密切相关。有趣的是,在免疫治疗反应组的患者中,LPCAT1 的表达水平通常较高。LPCAT1 和 PDL1 的联合表达可作为免疫治疗反应的有效预测指标。总之,LPCAT1 参与免疫调节和肿瘤进展,有望成为预测患者预后和免疫治疗疗效的生物标志物。

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