HMOX1 promotes lung adenocarcinoma metastasis by affecting macrophages and mitochondrion complexes.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.