Identification of crucial genes associated with lung adenocarcinoma by bioinformatic analysis

Abstract

Lung cancer is the world's most common malignancies and ranks first among all cancer-related deaths. Lung adenocarcinoma (LUAD) is the most frequent histological type in lung cancer. Its pathogenesis has not yet been fully elucidated, so it is of great significance to explore related genes for elucidating the molecular mechanism involved in occurrence and development of LUAD. To explore the crucial genes associated with LUAD development and progression, microarray datasets GSE7670, GSE10072, and GSE31547 were acquired from the Gene Expression Omnibus (GEO) database. R language Limma package was adopted to screen the differentially expressed genes (DEGs). The clusterProfiler package was used for enrichment analysis and annotation of the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways for DEGs. The Search Tool for the Retrieval of Interacting Genes database (STRING) was used to construct the protein interaction network for DEGs, while Cytoscape was adopted to visualize it. The functional module was screened with Cytoscape's MCODE (The Molecular Complex Detection) plugin. The crucial genes associated with LUAD were identified by cytoHubba plugin. Kaplan–Meier plotter online tool was used to perform survival analysis of the hub gene. Three hundred twenty-one DEGs in total were screened, of which 105 were upregulated and 216 were downregulated. It was found that some GO terms and pathways (e.g., collagen trimer, extracellular structure organization, heparin binding, complement and coagulation cascades, malaria, protein digestion and absorption, and PPAR signaling pathway) were considerably enriched in DEGs. UBE2C, TOP2A, RRM2, CDC20, CCNB2, KIAA0101, BUB1B, TPX2, PRC1, and CDK1 were identified as crucial genes. Survival analysis showed that the overexpression of UBE2C, TOP2A, RRM2, CDC20, CCNB2, KIAA0101, BUB1B, TPX2, and PRC1 significantly reduced the overall survival of LUAD patients. One of the crucial genes: UBE2C was validated by immunohistochemistry to be upregulated in LUAD tissues. This study screened out potential biomarkers of LUAD, providing a theoretical basis for elucidating the pathogenesis and evaluating the prognosis of LUAD.

AURKA, TOP2A and MELK are the key genes identified by WGCNA for the pathogenesis of lung adenocarcinoma

“…Etoposide, which targets TOP2A, has been approved for the treatment of small cell lung cancer, but there are currently no drugs for LUAD (48,49). Through various bioinformatics approaches, TOP2A has been identified as an independent factor affecting the prognosis of patients with LUAD (50)(51)(52)(53), whereas an increased TOP2A expression has also been identified as a potential risk factor for pathological stage I LUAD (54). Ciclopirox olamine and quercetin have also been demonstrated to exert tumor-suppressive effects via TOP2A in LUAD (55,56).…”

Circular RNA‐mediated ceRNA network was identified in human lung adenocarcinoma by high‐throughput sequencing

“…Meanwhile, tumor cell apoptosis increased. According to various studies, RRM2 can also be used as a target for antilung cancer drugs 28 . IGF2BP3 is a member of the IGF2BPs family, which are consider having a marked impact on cancer occurrence and development.…”

“…According to various studies, RRM2 can also be used as a target for antilung cancer drugs. 28 IGF2BP3 is a member of the IGF2BPs family, which are consider having a marked impact on cancer occurrence and development. Guo et al found that IGF2BP3 was abnormally highly expressed in LUAD and this could lead to a weaker prognosis ( p < 0.05).…”

Network module function enrichment analysis of lung squamous cell carcinoma and lung adenocarcinoma

“…[ 27 ] BUB1B overexpression significantly reduces OS in LUAD patients. [ 28 ] In addition, UBE2C expression is associated with poor LUAD patients’ prognosis undergoing surgery. [ 29 ] In gastric cancer, overexpression of the mitotic checkpoint gene BUB1 is associated with tumor cell proliferation and gastric cancer progression.…”