Identification of candidate genes associated with the pathogenesis of small cell lung cancer via integrated bioinformatics analysis

Abstract

The pathogenesis of small cell lung cancer (SCLC), a highly metastatic malignant tumor, remains unclear. In the present study, important genes and pathways that are involved in the pathogenesis of SCLC were identified. The following four datasets were downloaded from the Gene Expression Omnibus: GSE60052, GSE43346, GSE15240 and GSE6044. The differentially expressed genes (DEGs) between the SCLC samples and the normal samples were analyzed using R software. The limma package was used for every dataset. The RobustRankAggreg package was used to integrate the DEGs from the four datasets. Functional and pathway enrichment analyses were conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases with FunRich software and R software, respectively. In addition, the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database and Cytoscape software. Hub genes and significant modules were identified using Molecular Complex Detection in Cytoscape software. Finally, the expression values of hub genes were determined using the Oncomine online database. In total, 412 DEGs were identified following the integration of the four datasets, with 146 upregulated genes and 266 downregulated genes. The upregulated DEGs were primarily enriched in the cell cycle, cell division and microtubule binding. The downregulated DEGs were primarily enriched in the complement and coagulation cascades, the cytokine-mediated signaling pathway and protein binding. Eight hub genes and 1 significant module correlated to the cell cycle pathway were identified based on a subset of the PPI network. Finally, five hub genes were identified as highly expressed in SCLC tissue compared with normal tissue. The cell cycle pathway may be the pathway most closely associated with the pathogenesis of SCLC. NDC80, BUB1B, PLK1, CDC20 and MAD2L1 should be the focus of follow-up studies regarding the diagnosis and treatment of SCLC.

Analysis of the Expression of Cell Division Cycle-Associated Genes and Its Prognostic Significance in Human Lung Carcinoma: A Review of the Literature Databases

“…According to our results, attention should be paid to some pathways including R-HAS-2500257: resolution of sister chromatid cohesion; GO: 0051301: cell division; CORUM: 1118: chromosomal passenger complex (CPC, including CDCA8, INCENP, AURKB, and BIRC5); CORUM: 127: NDC80 kinetochore complex; M129: PID PLK1 pathway; and GO: 0007080: mitotic metaphase plate congression. Previous studies show that the Polo-like kinase 1(PLK1) is highly expressed in LC, which predicts the poor survival in metastatic LC patients [56,57]. In addition, the PLK1 pathway plays a certain role in the progression of HCC [58], glioma [59], and lung adenocarcinoma [60].…”

Potential therapeutic targets of the nuclear division cycle 80 (NDC80) complexes genes in lung adenocarcinoma

“…Lack of biomarkers of early diagnosis due to the occultation process, about 50% of patients with at the time of LUAD diagnosis has local infiltration and distant metastasis. The 5-year survival rate of clinical-stage 4 patients is less than 1% [3,5,6].…”

Identification of potential biomarkers or therapeutic targets of mesenchymal stem cells in multiple myeloma by bioinformatics analysis

“…As for MAD2L1, CCNB1, CDCA8, CDC20 and NDC80, these hub genes also played important roles in regulating cell proliferation, apoptosis and chromosome stability according to pervious reports [26,27]. The irregular expression of these genes in cells often accompanied with cell proliferation disorders and chromosome instability [28][29][30].…”