APOA1 promotes tumor proliferation and migration and may be a potential pan-cancer biomarker and immunotherapy target

IF 5 2区 医学 Q2 Medicine Translational Oncology Pub Date : 2025-05-01 Epub Date: 2025-03-14 DOI:10.1016/j.tranon.2025.102344
Peiyi Xu , Qiuyan Zhang , Jing Zhai, Pu Chen, Xueting Deng, Lin Miao, Xiuhua Zhang
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Abstract

Introduction

Aberrant expression of APOA1 has been reported in various cancers. However, a comprehensive investigation into its role in cancer is currently lacking.

Methods

Online websites and databases such as TIMER2.0, GEPIA2, UALCAN and GSCA were used to investigate the relationship between APOA1 expression and prognostic value, immune infiltration, gene mutations, and drug sensitivity. In addition, in vitro CCK-8 and transwell migration and invasion assays were performed to determine the biological functions of APOA1 in gastric cancer (GC) cells.

Results

The pan-cancer analysis showed that APOA1 is differentially expressed in different cancer types and significantly correlated with tumor stages. A survival analysis revealed that APOA1 predicted a poor prognosis in ACC, KIRC, STAD, and a good prognosis in BRCA, OV, and UCEC. We also found that the most common genetic alteration type of APOA1 was deep deletion, and the DNA methylation level of APOA1 decreased in various cancers. Furthermore, APOA1 expression negatively correlated with immune cells infiltration in cancers, including CD4+ T, CD8+ T, and myeloid dendritic cells. For STAD, GO/KEGG enrichment analysis revealed the possible involvement of APOA1 in cholesterol metabolism and PPAR signaling pathway. Finally, we further performed in vitro experiments to verify that overexpression of APOA1 could promote the proliferation, migration and invasion of GC cells.

Conclusion

The results of this study indicate that APOA1 is a potential tumor prognostic biomarker and immunotherapy target. In addition, APOA1 plays an essential role in the proliferation, migration, and invasion of GC cells by vitro experiments.
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APOA1促进肿瘤增殖和迁移,可能是潜在的泛癌症生物标志物和免疫治疗靶点
APOA1的异常表达在多种癌症中都有报道。然而,目前还缺乏对其在癌症中的作用的全面调查。方法利用TIMER2.0、GEPIA2、UALCAN、GSCA等在线网站和数据库,研究APOA1表达与预后价值、免疫浸润、基因突变、药物敏感性的关系。此外,通过体外CCK-8和跨井迁移和侵袭实验,确定APOA1在胃癌(GC)细胞中的生物学功能。结果泛癌分析显示,APOA1在不同类型肿瘤中有差异表达,且与肿瘤分期有显著相关性。一项生存分析显示,APOA1在ACC、KIRC、STAD中预测预后差,而在BRCA、OV和UCEC中预测预后好。我们还发现,APOA1最常见的遗传改变类型是深度缺失,APOA1的DNA甲基化水平在各种癌症中都有所下降。此外,APOA1的表达与免疫细胞浸润呈负相关,包括CD4+ T、CD8+ T和骨髓树突状细胞。对于STAD, GO/KEGG富集分析揭示了APOA1可能参与胆固醇代谢和PPAR信号通路。最后,我们进一步进行了体外实验,验证了APOA1过表达能够促进GC细胞的增殖、迁移和侵袭。结论APOA1是一种潜在的肿瘤预后生物标志物和免疫治疗靶点。此外,APOA1在体外实验中对GC细胞的增殖、迁移和侵袭起着重要的作用。
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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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