Joint multi-omics screening of neutrophil-related biomarkers for lung adenocarcinoma

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Abstract Objectives Neutrophils play a crucial part in the proliferation, migration, and invasion of a variety of cancers. Multi-omics approach was applied to explore the role of neutrophils in lung adenocarcinoma (LUAD) and their influence on LUAD progression was characterized. Methods The Cancer Genome Atlas Program (TCGA) database was accessed to obtain relevant data, based on which neutrophil subsets were identified after cell clustering and annotation using FindNeighbors and FindClusters. Monocle2 was utilized for Pseudotime analysis. Transcription factor (TF) prediction analysis was performed by applying pySCENIC. Hub genes identified by WGCNA were intersected with the genes screened by Cox regression to select key genes for LUAD. In addition, the expression and potential biological functions of the screened genes in LUAD were verified by conducting quantitative reverse transcription polymerase chain reaction (qRT-PCR), wound healing, and transwell assays. Results This study identified four neutrophil subsets, namely, Neu0, Neu1, Neu2, and Neu3. Pseudotime results revealed that the cells had five states, and cell communication analysis demonstrated a correlation between neutrophils and tumor cells. WGCNA analysis screened 381 hub genes, which were further compressed to 15 key genes. In vitro experiments validated the potential of the top five genes (P2RY13, CYTIP, ZYX, KLRB1, and HMOX1) to serve as biomarkers for LUAD. Knocking down HMOX1 effectively inhibited LUAD cell invasion and migration. Analysis of the prognostic models showed that the RiskScore and nomogram had strong prediction capabilities. Drug sensitivity analysis predicted vincristine as a potential drug for LUAD. Conclusions This study identified five neutrophil-related biomarkers (P2RY13, CYTIP, ZYX, KLRB1, and HMOX1) for LUAD. Importantly, HMOX1 affected LUAD cell invasion and migration. The present findings improved the current understanding of the pathogenesis of LUAD.