Chen Bo, Zhang Liyang, Zhou Hongshu, Ye Wenrui, Luo Cong, Yang Liting, Fang Ning, Tang Anliu
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2022 Aug 12;12:978006. doi: 10.3389/fonc.2022.978006. eCollection 2022.
Metastasis is the leading cause of lung adenocarcinoma (LUAD) patient death. However, the mechanism of metastasis is unclear. We performed bioinformatic analyses for HMOX1 (Heme oxygenase-1), aiming to explore its role in LUAD metastasis.
Pan-cancer analysis was first used to identify the metastasis-associated role of HMOX1 in LUAD. HMOX1-related genomic alterations were then investigated. Based on functional enrichment, we systematically correlated HMOX1 with immunological characteristics and mitochondrial activities. Furthermore, weighted gene co-expression network analysis (WGCNA) was applied to construct the HMOX1-mediated metastasis regulatory network, which was then validated at the proteomic level. Finally, we conducted the survival analysis and predicted the potential drugs to target the HMOX1 network.
HMOX1 expression was significantly associated with epithelial-mesenchymal transition (EMT) and lymph and distant metastasis in LUAD. High HMOX1 levels exhibited higher macrophage infiltration and lower mitochondrial complex expression. WGCNA showed a group of module genes co-regulating the traits mentioned above. Subsequently, we constructed an HMOX1-mediated macrophage-mitochondrion-EMT metastasis regulatory network in LUAD. The network had a high inner correlation at the proteomic level and efficiently predicted prognosis. Finally, we predicted 9 potential drugs targeting HMOX1-mediated metastasis in LUAD, like chloroxine and isoliquiritigenin.
Our analysis elaborates on the role of HMOX1 in LUAD metastasis and identified a highly prognostic HMOX1-mediated metastasis regulatory network. Novel potential drugs targeting the HMOX1 network were also proposed, which should be tested for their activity against LUAD metastasis in future studies.
转移是肺腺癌（LUAD）患者死亡的主要原因。然而，转移机制尚不清楚。我们对HMOX1（血红素加氧酶-1）进行了生物信息学分析，旨在探讨其在LUAD转移中的作用。
首先进行泛癌分析，以确定HMOX1在LUAD中的转移相关作用。然后研究与HMOX1相关的基因组改变。基于功能富集，我们系统地将HMOX1与免疫特征和线粒体活性相关联。此外，应用加权基因共表达网络分析（WGCNA）构建HMOX1介导的转移调控网络，然后在蛋白质组水平进行验证。最后，我们进行了生存分析，并预测了靶向HMOX1网络的潜在药物。
HMOX1表达与LUAD中的上皮-间质转化（EMT）以及淋巴和远处转移显著相关。HMOX1水平高表现出更高的巨噬细胞浸润和更低的线粒体复合物表达。WGCNA显示一组模块基因共同调节上述特征。随后，我们构建了LUAD中HMOX1介导的巨噬细胞-线粒体-EMT转移调控网络。该网络在蛋白质组水平具有高度的内部相关性，并能有效预测预后。最后，我们预测了9种靶向LUAD中HMOX1介导转移的潜在药物，如氯氧嗪和异甘草素。
我们的分析阐述了HMOX1在LUAD转移中的作用，并确定了一个具有高度预后价值的HMOX1介导的转移调控网络。还提出了靶向HMOX1网络的新型潜在药物，应在未来研究中测试其对LUAD转移的活性。
