Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Parasitology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
Zhuzhou Central Hospital, The Affiliated Zhuzhou Hospital, Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.
Cancer Immunol Immunother. 2022 Oct;71(10):2449-2467. doi: 10.1007/s00262-022-03167-8. Epub 2022 Mar 7.
Histone lysine demethylases (KDMs) are closely related to the occurrence and development of different tumors through epigenetic mechanisms. However, the prognosis and immune infiltration of KDMs in hepatocellular carcinoma (HCC) remain undefined.
In the current study, we analyzed the expression of KDMs on HCC patients using the Oncomine, GEPIA, UALCAN, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, Metascape, GSEA, and TIMER databases. Finally, we investigated KDM expression in HCC by qRT-PCR, Western blotting, and IHC.
We found that KDM3A/3B/5A/5B and KDM6A were upregulated in HCC patients, while KDM6B and KDM8 were downregulated. The high expressions of KDM1A/2B/3B/5B/5C were markedly related to tumor stages and grades of HCC patients. The abnormal expression of KDM1A/1B/3A/4A/5A/5C/6A/6B/7A and KDM8 were associated with HCC patients' prognosis. Also, we found that HCC tissues presented higher expression levels of KDM1A/2A/5A/5B and lower expression levels of KDM6B. The function of KDMs was primarily related to the histone demethylase activity and cell cycle, p53 signaling pathway, pathways in cancer, transcriptional mis-regulation in cancer, viral carcinogenesis, and FoxO signaling pathway. Furthermore, we indicated that the pathways most involved were the mitotic spindle and DNA repair. Additionally, we found that the expression of KDM1A/1B/3A/4A/5B/5C and KDM6A were significantly correlated with HCC immune infiltration.
Overall, our current results indicated that KDM1A/1B/3A/4A/5B/5C and KDM6A could be novel prognostic biomarkers and provide insights into potential immunotherapy targets to HCC patients.
组蛋白赖氨酸去甲基酶（KDMs）通过表观遗传机制与不同肿瘤的发生和发展密切相关。然而，KDMs 在肝细胞癌（HCC）中的预后和免疫浸润仍未确定。
在本研究中，我们使用 Oncomine、GEPIA、UALCAN、Kaplan-Meier Plotter、cBioPortal、GeneMANIA、STRING、Metascape、GSEA 和 TIMER 数据库分析了 HCC 患者中 KDMs 的表达。最后，我们通过 qRT-PCR、Western blot 和 IHC 检测了 HCC 中的 KDM 表达。
我们发现 KDM3A/3B/5A/5B 和 KDM6A 在 HCC 患者中上调，而 KDM6B 和 KDM8 下调。KDM1A/2B/3B/5B/5C 的高表达与 HCC 患者的肿瘤分期和分级明显相关。KDM1A/1B/3A/4A/5A/5C/6A/6B/7A 和 KDM8 的异常表达与 HCC 患者的预后相关。此外，我们发现 HCC 组织中 KDM1A/2A/5A/5B 的表达水平较高，而 KDM6B 的表达水平较低。KDMs 的功能主要与组蛋白去甲基酶活性和细胞周期、p53 信号通路、癌症途径、转录失调致癌、病毒致癌和 FoxO 信号通路有关。此外，我们表明最相关的途径是有丝分裂纺锤体和 DNA 修复。此外，我们发现 KDM1A/1B/3A/4A/5B/5C 和 KDM6A 的表达与 HCC 免疫浸润显著相关。
总的来说，我们目前的研究结果表明，KDM1A/1B/3A/4A/5B/5C 和 KDM6A 可能是新的预后生物标志物，并为 HCC 患者提供了潜在的免疫治疗靶点的见解。
