ATP13A2 是肝细胞癌的预后生物标志物，并与免疫浸润相关。

ATP13A2 is a Prognostic Biomarker and Correlates with Immune Infiltrates in Hepatocellular Carcinoma.

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian Province, China.

Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.

出版信息

J Gastrointest Surg. 2023 Jan;27(1):56-66. doi: 10.1007/s11605-021-05099-7. Epub 2022 Sep 20.

DOI:10.1007/s11605-021-05099-7

PMID:36127552

Abstract

PURPOSE

To explore the expression and role of ATPase cation transporting 13A2 (ATP13A2) on hepatocellular carcinoma (HCC) progression and prognosis.

METHODS

The level of ATP13A2 in 63 HCC tissues was evaluated by quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry. Then, the prognostic value of ATP13A2 for HCC was explored. GO and KEGG pathway enrichments were performed to predict ATP13A2-mediated biological functions. Besides, the correlations between ATP13A2 and key regulators involved in cell cycle and metastasis, the status of different tumor-infiltrating immune cells was investigated.

RESULTS

ATP13A2 was frequently upregulated in 63 HCC tissues relatively to matched non-tumor tissues. The level of ATP13A2 significantly correlated with tumor stage and tumor grade. HCC patients with higher levels of ATP13A2 had a worse prognosis. Moreover, multivariate survival analysis supported ATP13A2 to be an independent prognostic factor for HCC. GO and KEGG analysis indicated a potential role of ATP13A2 on regulating cell cycle, metastasis, and immune infiltrates. Especially, the level of ATP13A2 was positively correlated with CCNB1, CCND3, CDC25B, CDK4, Vimentin, MMP9, MMP14, and LMNB2. A positive correlation was noticed between ATP13A2 and infiltration levels of B cells, CD8 T cells, CD4 T cells, macrophages, neutrophils, dendritic cells, monocytes, M2 macrophages, and exhausted T cells in HCC.

CONCLUSION

Upregulation of ATP13A2 is a common feature as well as an independent prognostic biomarker for HCC. ATP13A2 are associated with key regulators involved in cell cycle, metastasis, and immune infiltrates in HCC, and may act as a potential immunotherapy target for HCC.

摘要

目的

探讨三磷酸腺苷酶阳离子转运体 13A2（ATP13A2）在肝细胞癌（HCC）进展和预后中的表达和作用。

方法

通过定量实时聚合酶链反应、Western blot 和免疫组织化学评估 63 例 HCC 组织中 ATP13A2 的水平。然后，探讨 ATP13A2 对 HCC 的预后价值。进行 GO 和 KEGG 通路富集，以预测 ATP13A2 介导的生物学功能。此外，还研究了 ATP13A2 与涉及细胞周期和转移的关键调节剂之间的相关性，以及不同肿瘤浸润免疫细胞的状态。

结果

ATP13A2 在 63 例 HCC 组织中相对于匹配的非肿瘤组织频繁上调。ATP13A2 的水平与肿瘤分期和肿瘤分级显著相关。ATP13A2 水平较高的 HCC 患者预后较差。此外，多变量生存分析支持 ATP13A2 是 HCC 的独立预后因素。GO 和 KEGG 分析表明，ATP13A2 在调节细胞周期、转移和免疫浸润方面具有潜在作用。特别是，ATP13A2 的水平与 CCNB1、CCND3、CDC25B、CDK4、波形蛋白、MMP9、MMP14 和 LMNB2 呈正相关。在 HCC 中，还观察到 ATP13A2 与 B 细胞、CD8 T 细胞、CD4 T 细胞、巨噬细胞、中性粒细胞、树突状细胞、单核细胞、M2 巨噬细胞和耗竭 T 细胞浸润水平呈正相关。