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

IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hongyu Gao, Jinfeng Zhu, Tong Wu, Qian Long, Xinyu Guan, Qitong Chen, Wenjun Yi
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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.

Abstract Image

胰腺癌综合分析表明,LPCAT1 是预测预后和免疫疗法反应的新型生物标志物。
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,对维持生物膜的结构和功能至关重要。然而,目前还缺乏对 LPCAT1 在各种癌症类型中作用的全面研究。我们利用多个公共数据库研究了不同癌症类型中 LPCAT1 的表达、基因改变、甲基化、预后、生物功能及其与抗肿瘤免疫的关系。体外实验进一步验证了 LPCAT1 在胶质瘤、乳腺癌和肝癌细胞中的功能。我们的研究表明,LPCAT1 在各种癌症中均呈上调趋势,并伴有多种扩增突变。在多种癌症中,LPCAT1的高表达与较差的预后有关。进一步的体外实验表明,干扰 LPCAT1 的表达可增加胶质瘤、乳腺癌和肝癌细胞的凋亡,同时抑制它们的增殖和迁移。功能富集分析显示,LPCAT1相关基因主要富集于免疫和癌症进展通路,如JAK/STAT、MYC和EMT等。此外,LPCAT1的表达与免疫细胞浸润和免疫检查点相关基因的表达密切相关。有趣的是,免疫治疗反应组患者的LPCAT1表达水平普遍较高。LPCAT1 和 PDL1 的结合可有效预测免疫治疗反应。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疗法疗效的生物标记物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Apoptosis
Apoptosis 生物-生化与分子生物学
CiteScore
9.10
自引率
4.20%
发文量
85
审稿时长
1 months
期刊介绍: Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.
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