Mosharaf Md Parvez, Reza Md Selim, Gov Esra, Mahumud Rashidul Alam, Mollah Md Nurul Haque
Bioinformatics Lab, Department of Statistics, University of Rajshahi, Rajshahi 6205, Bangladesh.
School of Commerce, Faculty of Business, Education, Law and Arts, University of Southern Queensland, Toowoomba, QLD 4350, Australia.
Vaccines (Basel). 2022 May 12;10(5):771. doi: 10.3390/vaccines10050771.
Non-small-cell lung cancer (NSCLC) is considered as one of the malignant cancers that causes premature death. The present study aimed to identify a few potential novel genes highlighting their functions, pathways, and regulators for diagnosis, prognosis, and therapies of NSCLC by using the integrated bioinformatics approaches. At first, we picked out 1943 DEGs between NSCLC and control samples by using the statistical LIMMA approach. Then we selected 11 DEGs (, , , , , , , , , , and ) as the hub-DEGs (potential key genes) by the protein-protein interaction network analysis of DEGs. The DEGs and hub-DEGs regulatory network analysis commonly revealed four transcription factors (, , , and and five miRNAs (miR-335-5p, miR-26b-5p, miR-92a-3p, miR-155-5p, and miR-16-5p) as the key transcriptional and post-transcriptional regulators of DEGs as well as hub-DEGs. We also disclosed the pathogenetic processes of NSCLC by investigating the biological processes, molecular function, cellular components, and KEGG pathways of DEGs. The multivariate survival probability curves based on the expression of hub-DEGs in the SurvExpress web-tool and database showed the significant differences between the low- and high-risk groups, which indicates strong prognostic power of hub-DEGs. Then, we explored top-ranked 5-hub-DEGs-guided repurposable drugs based on the Connectivity Map (CMap) database. Out of the selected drugs, we validated six FDA-approved launched drugs (Dinaciclib, Afatinib, Icotinib, Bosutinib, Dasatinib, and TWS-119) by molecular docking interaction analysis with the respective target proteins for the treatment against NSCLC. The detected therapeutic targets and repurposable drugs require further attention by experimental studies to establish them as potential biomarkers for precision medicine in NSCLC treatment.
非小细胞肺癌(NSCLC)被认为是导致过早死亡的恶性肿瘤之一。本研究旨在通过综合生物信息学方法,鉴定一些潜在的新基因,突出它们在NSCLC诊断、预后和治疗方面的功能、途径及调控因子。首先,我们使用统计LIMMA方法在NSCLC与对照样本之间筛选出1943个差异表达基因(DEGs)。然后,通过对DEGs进行蛋白质-蛋白质相互作用网络分析,我们选择了11个DEGs(,,,,,,,,,,和)作为枢纽DEGs(潜在关键基因)。对DEGs和枢纽DEGs调控网络分析共同揭示了四个转录因子(,,,和)以及五个微小RNA(miR-335-5p、miR-26b-5p、miR-92a-3p、miR-155-5p和miR-16-5p)作为DEGs以及枢纽DEGs的关键转录和转录后调控因子。我们还通过研究DEGs的生物学过程、分子功能、细胞成分和KEGG途径,揭示了NSCLC的发病机制。基于SurvExpress网络工具和数据库中枢纽DEGs的表达绘制的多变量生存概率曲线显示,低风险组和高风险组之间存在显著差异,这表明枢纽DEGs具有强大的预后能力。然后,我们基于连通性图谱(CMap)数据库探索了排名前5的枢纽DEGs指导的可重新利用药物。在所选药物中,我们通过与各自靶蛋白的分子对接相互作用分析,验证了6种美国食品药品监督管理局(FDA)批准上市的药物(地西他滨、阿法替尼、埃克替尼、博舒替尼、达沙替尼和TWS-119)用于治疗NSCLC。检测到的治疗靶点和可重新利用药物需要进一步的实验研究关注,以将它们确立为NSCLC治疗精准医学的潜在生物标志物。