Identification of Potential Key Genes and Prognostic Biomarkers of Lung Cancer Based on Bioinformatics

Cai, Kaier; Xie, Zhen; Liu, Yingao; Wu, Jerry J.; Song, Hongjiang; Liu, Wang; Wang, Xinyi; Xiong, Yinghuan; Gan, Siyuan; Sun, Yanqin

doi:10.1155/2023/2152432

Cited by 2 publications

(1 citation statement)

References 37 publications

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“…Hence, CDK1 may be used as potential biomarkers and therapeutic targets for LUAD [61].Checkpoint kinase 1 (CHEK1, also known as CHK1) is a conserved serine/ threonine kinase that plays an important role in replication fork stability and DNA damage response [62]. In a study of TP53 mutant NSCLC tumor cells, it was found that inhibiting the expression of CHEK1 can significantly enhance the sensitivity of tumor cells to chemotherapy [63,64]. In addition, promoter methylation, amplification, and miRNA regulation in patients with lung adenocarcinoma may lead to the upregulation of the CHEK1 gene, which may be a marker for predicting the survival rate of patients with lung adenocarcinoma [65].…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of 6-Methoxydihydrosanguinarine in the treatment of lung adenocarcinoma based on network pharmacology, molecular docking and experimental investigation

Liu,

Ren,

Qin

et al. 2024

BMC Complement Med Ther

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Background 6-Methoxydihydrosanguinarine (6-MDS) has shown promising potential in fighting against a variety of malignancies. Yet, its anti‑lung adenocarcinoma (LUAD) effect and the underlying mechanism remain largely unexplored. This study sought to explore the targets and the probable mechanism of 6-MDS in LUAD through network pharmacology and experimental validation. Methods The proliferative activity of human LUAD cell line A549 was evaluated by Cell Counting Kit-8 (CCK8) assay. LUAD related targets, potential targets of 6-MDS were obtained from databases. Venn plot analysis were performed on 6-MDS target genes and LUAD related genes to obtain potential target genes for 6-MDS treatment of LUAD. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was utilized to perform a protein-protein interaction (PPI) analysis, which was then visualized by Cytoscape. The hub genes in the network were singled out by CytoHubba. Metascape was employed for GO and KEGG enrichment analyses. molecular docking was carried out using AutoDock Vina 4.2 software. Gene expression levels, overall survival of hub genes were validated by the GEPIA database. Protein expression levels, promotor methylation levels of hub genes were confirmed by the UALCAN database. Timer database was used for evaluating the association between the expression of hub genes and the abundance of infiltrating immune cells. Furthermore, correlation analysis of hub genes expression with immune subtypes of LUAD were performed by using the TISIDB database. Finally, the results of network pharmacology analysis were validated by qPCR. Results Experiments in vitro revealed that 6-MDS significantly reduced tumor growth. A total of 33 potential targets of 6-MDS in LUAD were obtained by crossing the LUAD related targets with 6-MDS targets. Utilizing CytoHubba, a network analysis tool, the top 10 genes with the highest centrality measures were pinpointed, including MMP9, CDK1, TYMS, CCNA2, ERBB2, CHEK1, KIF11, AURKB, PLK1 and TTK. Analysis of KEGG enrichment hinted that these 10 hub genes were located in the cell cycle signaling pathway, suggesting that 6-MDS may mainly inhibit the occurrence of LUAD by affecting the cell cycle. Molecular docking analysis revealed that the binding energies between 6-MDS and the hub proteins were all higher than − 6 kcal/Mol with the exception of AURKB, indicating that the 9 targets had strong binding ability with 6-MDS.These results were corroborated through assessments of mRNA expression levels, protein expression levels, overall survival analysis, promotor methylation level, immune subtypes andimmune infiltration. Furthermore, qPCR results indicated that 6-MDS can significantly decreased the mRNA levels of CDK1, CHEK1, KIF11, PLK1 and TTK. Conclusions According to our findings, it appears that 6-MDS could possibly serve as a promising option for the treatment of LUAD. Further investigations in live animal models are necessary to confirm its potential in fighting cancer and to delve into the mechanisms at play.

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