Abstract
PurposeExploring the molecular mechanisms of lung adenocarcinoma (LUAD) is beneficial for developing new therapeutic strategies and predicting prognosis. This study was performed to select core genes related to LUAD and to analyze their prognostic value.MethodsMicroarray datasets from the GEO (GSE75037) and TCGA-LUAD datasets were analyzed to identify differentially coexpressed genes in LUAD using weighted gene coexpression network analysis (WGCNA) and differential gene expression analysis. Functional enrichment analysis was conducted, and a protein–protein interaction (PPI) network was established. Subsequently, hub genes were identified using the CytoHubba plug-in. Overall survival (OS) analyses of hub genes were performed. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (THPA) databases were used to validate our findings. Gene set enrichment analysis (GSEA) of survival-related hub genes were conducted. Immunohistochemistry (IHC) was carried out to validate our findings.ResultsWe identified 486 differentially coexpressed genes. Functional enrichment analysis suggested these genes were primarily enriched in the regulation of epithelial cell proliferation, collagen-containing extracellular matrix, transforming growth factor beta binding, and signaling pathways regulating the pluripotency of stem cells. Ten hub genes were detected using the maximal clique centrality (MCC) algorithm, and four genes were closely associated with OS. The CPTAC and THPA databases revealed that CHRDL1 and SPARCL1 were downregulated at the mRNA and protein expression levels in LUAD, whereas SPP1 was upregulated. GSEA demonstrated that DNA-dependent DNA replication and catalytic activity acting on RNA were correlated with CHRDL1 and SPARCL1 expression, respectively. The IHC results suggested that CHRDL1 and SPARCL1 were significantly downregulated in LUAD.ConclusionsOur study revealed that survival-related hub genes closely correlated with the initiation and progression of LUAD. Furthermore, CHRDL1 and SPARCL1 are potential therapeutic and prognostic indicators of LUAD.
Highlights
As one of common cancers, lung carcinoma was estimated to have caused disease in 235,760 patients and 131,880 deaths in 2021, resulting in a tremendous burden to our society [1]
Our study revealed that survival-related hub genes closely correlated with the initiation and progression of lung adenocarcinoma (LUAD)
Identification of core coexpression modules through Weighed gene coexpression network analysis (WGCNA) To detect the functional modules in LUAD, we established two gene coexpression networks using the GSE75037 and The Cancer Genome Atlas database (TCGA)-LUAD datasets through the WGCNA package in R software
Summary
As one of common cancers, lung carcinoma was estimated to have caused disease in 235,760 patients and 131,880 deaths in 2021, resulting in a tremendous burden to our society [1]. Deng et al Cancer Cell Int (2021) 21:259 accounted for nearly 85% of all patients with lung cancer, and the most prevalent pathological pattern of NSCLC was lung adenocarcinoma (LUAD) [2]. Many researchers have concentrated on studying the potential biological and molecular mechanisms of lung cancer, and the molecular mechanisms are gradually being understood [3]. With the rapid advancement of genomic technology, bioinformatics analyses have been widely used in the analysis of microarray datasets to further study the potential molecular mechanisms of cancers and to identify tumor-specific indicators [5]. Differential gene expression analysis is usually used in transcriptomics datasets to study underlying biological and molecular mechanisms and to identify quantitative differences in the expression level of the gene between different groups [8]
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