Zhou Lingyi, Fu Zheng, Wang Shuai, Jia Jing, Cheng Yumeng, Zheng Yunxiang, Zhang Ningning, Lu Wei, Yao Zhi
Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Innovation and R&D Management Department, Tianjin Kangzhe Pharmaceutical Technology Development Company, Ltd., Tianjin, China.
Front Oncol. 2022 May 2;12:875097. doi: 10.3389/fonc.2022.875097. eCollection 2022.
ACYP1 plays important physiological and metabolic roles in glycolysis and membrane ion pump activity by catalyzing acyl phosphate hydrolysis. ACYP1 is related to tumorigenesis and progression and poor prognosis in gastrointestinal cancer. However, its pancancer roles and mechanisms are unclear. Our study aimed to understand the ACYP1 expression signature and prognostic value across cancers and investigate immune infiltration patterns in liver hepatocellular carcinoma (LIHC) and verify them in LIHC samples.
Transcriptional expression profiles of ACYP1 across cancers were analyzed using Oncomine and TIMER. The prognostic value of ACYP1 was assessed across PrognoScan, Kaplan-Meier Plotter, and GEPIA. Significant pathways associated with ACYP1 in LIHC were obtained Gene Set Enrichment Analysis. The correlation between ACYP1 expression and immune infiltration in LIHC was investigated using TIMER. We validated ACYP1 expression, prognostic value, and association with immune cells in tumor tissues by immunohistochemistry and flow cytometry.
ACYP1 was overexpressed across cancers. High expression of ACYP1 correlated with a poor prognosis in most tumor types, especially in LIHC. ACYP1 was significantly implicated in immune and metabolic related pathways. High ACYP1 expression showed significant correlations with the abundances of Th2 cells, Tregs, macrophages, dendritic cells, and myeloid-derived suppressor cells in LIHC. LIHC patients with high ACYP1 expression showed significantly shorter overall survival and relapse-free survival rates concomitant with increased infiltration of CD4+ T cells. Mouse subcutaneous tumors with ACYP1 overexpression exhibited significantly accelerated tumor progression with increased aggregation of CD4+ T cells.
Overall, ACYP1 may serve as a vital prognostic biomarker and play an immunoregulatory role in LIHC.
ACYP1通过催化酰基磷酸水解在糖酵解和膜离子泵活性中发挥重要的生理和代谢作用。ACYP1与胃肠道癌的肿瘤发生、进展及不良预后相关。然而，其在泛癌中的作用和机制尚不清楚。我们的研究旨在了解ACYP1在各种癌症中的表达特征和预后价值，并研究肝细胞癌（LIHC）中的免疫浸润模式，并在LIHC样本中进行验证。
使用Oncomine和TIMER分析ACYP1在各种癌症中的转录表达谱。通过PrognoScan、Kaplan-Meier Plotter和GEPIA评估ACYP1的预后价值。通过基因集富集分析获得与LIHC中ACYP1相关的重要通路。使用TIMER研究ACYP1表达与LIHC中免疫浸润的相关性。我们通过免疫组织化学和流式细胞术验证了肿瘤组织中ACYP1的表达、预后价值以及与免疫细胞的关联。
ACYP1在各种癌症中均有过表达。ACYP1的高表达与大多数肿瘤类型的不良预后相关，尤其是在LIHC中。ACYP1与免疫和代谢相关通路显著相关。ACYP1高表达与LIHC中Th2细胞、调节性T细胞、巨噬细胞、树突状细胞和髓源性抑制细胞的丰度显著相关。ACYP1高表达的LIHC患者总生存期和无复发生存期明显缩短，同时CD4+T细胞浸润增加。ACYP1过表达的小鼠皮下肿瘤表现出肿瘤进展明显加速，CD4+T细胞聚集增加。
总体而言，ACYP1可能是一种重要的预后生物标志物，并在LIHC中发挥免疫调节作用。
