Abstract
Purpose The molecular mechanism underlying the tumorigenesis and progression of lung adenocarcinoma (LUAD) in nonsmoking patients remains unclear. This study was conducted to select crucial therapeutic and prognostic biomarkers for nonsmoking patients with LUAD. Methods Microarray datasets from the Gene Expression Omnibus (GSE32863 and GSE75037) were analyzed for differentially expressed genes (DEGs). Gene Ontology (GO) enrichment analysis of DEGs was performed, and protein-protein interaction network was then constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. Hub genes were then identified by the rank of degree. Overall survival (OS) analyses of hub genes were performed among nonsmoking patients with LUAD in Kaplan-Meier plotter. The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (THPA) databases were applied to verify hub genes. In addition, we performed Gene Set Enrichment Analysis (GSEA) of hub genes. Results We identified 1283 DEGs, including 743 downregulated and 540 upregulated genes. GO enrichment analyses showed that DEGs were significantly enriched in collagen-containing extracellular matrix and extracellular matrix organization. Moreover, 19 hub genes were identified, and 12 hub genes were closely associated with OS. Although no obvious difference was detected in ITGB1, the downregulation of UBB and upregulation of RAC1 were observed in LUAD tissues of nonsmoking patients. Immunohistochemistry in THPA database confirmed that UBB and ITGB1 were downregulated, while RAC1 was upregulated in LUAD. GSEA suggested that ribosome, B cell receptor signaling pathway, and cell cycle were associated with UBB, RAC1, and ITGB1 expression, respectively. Conclusions Our study provides insights into the underlying molecular mechanisms of the carcinogenesis and progression of LUAD in nonsmoking patients and demonstrated UBB, RAC1, and ITGB1 as therapeutic and prognostic indicators for nonsmoking LUAD. This is the first study to report the crucial role of UBB in nonsmoking LUAD.
Highlights
Lung cancer (LC) is the most prevalent cancer type, with approximately 228,820 cancer cases and 135,720 death cases in 2020 worldwide, causing considerable socioeconomic burdens [1]
Gene Ontology (GO) enrichment analyses of downregulated differentially expressed genes (DEGs) revealed that collagen-containing extracellular matrix (ECM) was considerably enriched in biological processes (BP), extracellular structure organization in cellular component (CC), and ECM structural constituent in molecular function (MF) (Figure 2(a))
GO enrichment analyses of upregulated DEGs suggested that the ECM organization was primarily enriched in BP, apical plasma membrane in CC, and cell adhesion module binding in MF (Figure 2(b))
Summary
Lung cancer (LC) is the most prevalent cancer type, with approximately 228,820 cancer cases and 135,720 death cases in 2020 worldwide, causing considerable socioeconomic burdens [1]. Patients with non-small-cell lung cancer (NSCLC) constitute approximately 85% of the total LC cases. Lung adenocarcinoma (LUAD) is the most common histological type of NSCLC [2]. It is widely known that tobacco smoking is a crucial risk factor for LC; approximately 20% of LUAD cases occur among nonsmoking patients [3]. Patients with smoking-related LUAD have some altered genes such as KRAS and STK11. These known cancer-related genes may alter simultaneously, BioMed Research International leading to a larger tumor mutational burden (TMB) [4, 5]. The molecular mechanism underlying the carcinogenesis and progression of nonsmoking-related LUAD remains unclear. It is extremely necessary to identify key indicators in the carcinogenesis and development of nonsmoking-related LUAD
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
