Kim Hyung Suk, Son Byoung Kwan, Kwon Mi Jung, Kim Dong-Hoon, Min Kyueng-Whan
Department of Surgery, Division of Breast Surgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri 11923, Korea.
Department of Internal Medicine, Eulji Hospital, Eulji University School of Medicine, Seoul 03181, Korea.
J Clin Med. 2021 Mar 7;10(5):1112. doi: 10.3390/jcm10051112.
Lysine-specific demethylase 1A (KDM1A) plays an important role in epigenetic regulation in malignant tumors and promotes cancer invasion and metastasis by blocking the immune response and suppressing cancer surveillance activities. The aim of this study was to analyze survival, genetic interaction networks and anticancer immune responses in breast cancer patients with high KDM1A expression and to explore candidate target drugs.
We investigated clinicopathologic parameters, specific gene sets, immunologic relevance, pathway-based networks and in vitro drug response according to KDM1A expression in 456 and 789 breast cancer patients from the Hanyang university Guri Hospital (HYGH) and The Cancer Genome Atlas, respectively.
High KDM1A expression was associated with a low survival rate in patients with breast cancer. In analyses of immunologic gene sets, high KDM1A expression correlated with low immune responses. In silico flow cytometry results revealed low abundances of CD8+T cells and high programmed death-ligand 1 (PD-L1) expression in those with high KDM1A expression. High KDM1A expression was associated with a decrease in the anticancer immune response in breast cancer. In pathway-based networks, KDM1A was linked directly to pathways related to the androgen receptor signaling pathway and indirectly to the immune pathway and cell cycle. We found that alisertib effectively inhibited breast cancer cell lines with high KDM1A expression.
Strategies utilizing KDM1A may contribute to better clinical management/research for patients with breast cancer.
赖氨酸特异性去甲基化酶1A（KDM1A）在恶性肿瘤的表观遗传调控中起重要作用，并通过阻断免疫反应和抑制癌症监测活动促进癌症侵袭和转移。本研究的目的是分析KDM1A高表达的乳腺癌患者的生存情况、基因相互作用网络和抗癌免疫反应，并探索候选靶标药物。
我们分别根据来自汉阳大学九里医院（HYGH）的456例和癌症基因组图谱的789例乳腺癌患者的KDM1A表达情况，调查了临床病理参数、特定基因集、免疫相关性、基于通路的网络和体外药物反应。
KDM1A高表达与乳腺癌患者的低生存率相关。在免疫基因集分析中，KDM1A高表达与低免疫反应相关。计算机模拟流式细胞术结果显示，KDM1A高表达者的CD8 + T细胞丰度低，程序性死亡配体1（PD-L1）表达高。KDM1A高表达与乳腺癌的抗癌免疫反应降低有关。在基于通路的网络中，KDM1A直接与雄激素受体信号通路相关的通路相连，间接与免疫通路和细胞周期相连。我们发现阿利塞替布可有效抑制KDM1A高表达的乳腺癌细胞系。
利用KDM1A的策略可能有助于改善乳腺癌患者的临床管理/研究。
