Abstract
BackgroundUpregulation of the six-transmembrane epithelial antigen of prostate-1 (STEAP1) is closely associated with prognosis of numerous malignant cancers. However, its role in lung adenocarcinoma (LUAD), the most common type of lung cancer, remains unknown. This study aimed to investigate the role of STEAP1 in the occurrence and progression of LUAD and the potential mechanisms underlying its regulatory effects.MethodsSTEAP1 mRNA and protein expression were analyzed in 40 LUAD patients via real-time PCR and western blotting, respectively. We accessed the clinical data of 522 LUAD patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to investigate the expression and prognostic role of STEAP1 in LUAD. Further, we performed gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) to elucidate the potential mechanism underlying the role of STEAP1 in LUAD. The protein-protein interaction (PPI) network of STEAP1 was analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and hub genes with significant positive and negative associations with STEAP1 were identified and their role in LUAD prognosis was predicted.ResultsSTEAP1 was significantly upregulated in LUAD patients and associated with LUAD prognosis. Further, TCGA data indicated that STEAP1 upregulation is correlated with the clinical prognosis of LUAD. GO and KEGG analysis revealed that the genes co-expressed with STEAP1 were primarily involved in cell division, DNA replication, cell cycle, apoptosis, cytokine signaling, NF-kB signaling, and TNF signaling. GSEA revealed that homologous recombination, p53 signaling pathway, cell cycle, DNA replication, apoptosis, and toll-like receptor signaling were highly enriched upon STEAP1 upregulation. Gene Expression Profiling Interactive Analysis (GEPIA) analysis revealed that the top 10 hub genes associated with STEAP1 expression were also associated with the LUAD prognosis.ConclusionSTEAP1 upregulation potentially influences the occurrence and progression of LUAD and its co-expressed genes via regulation of homologous recombination, p53 signaling, cell cycle, DNA replication, and apoptosis. STEAP1 is a potential prognostic biomarker for LUAD.
Highlights
Lung cancer has one of the highest rates of incidence and mortality among all types of malignant tumors (Bray et al, 2018)
These results suggest that Lung adenocarcinoma (LUAD) patients with high six-transmembrane epithelial antigen of prostate1 (STEAP1) expression levels were more likely to have an advanced LUAD stage and a poor prognosis than those with low STEAP1 expression levels
We found that genes co-expressed with STEAP1 were primarily involved in cell adhesion, cell division, cytokine production, cytokine signaling, and DNA replication (Figures 4A–C)
Summary
Lung cancer has one of the highest rates of incidence and mortality among all types of malignant tumors (Bray et al, 2018). Lung adenocarcinoma (LUAD), the most common type of NSCLC and accounting for approximately 40% of all lung cancers, is one of the leading causes of respiratory cancer-associated deaths (Maemura et al, 2018; Kleczko et al, 2019). Owing to the insidious nature of NSCLC progression, most of the patients still present at an advanced stage upon diagnosis. Most of these patients cannot be surgically treated and respond poorly to radiotherapy and chemotherapy, resulting in a
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
