Department of Biology, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
Department of Health Ecosystem, Medical Faculty, Nisantasi University, Istanbul, Turkey.
Sci Rep. 2022 Jun 8;12(1):9417. doi: 10.1038/s41598-022-13719-8.
Lung cancer is the most common cancer in men and women. This cancer is divided into two main types, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Around 85 to 90 percent of lung cancers are NSCLC. Repositioning potent candidate drugs in NSCLC treatment is one of the important topics in cancer studies. Drug repositioning (DR) or drug repurposing is a method for identifying new therapeutic uses of existing drugs. The current study applies a computational drug repositioning method to identify candidate drugs to treat NSCLC patients. To this end, at first, the transcriptomics profile of NSCLC and healthy (control) samples was obtained from the GEO database with the accession number GSE21933. Then, the gene co-expression network was reconstructed for NSCLC samples using the WGCNA, and two significant purple and magenta gene modules were extracted. Next, a list of transcription factor genes that regulate purple and magenta modules' genes was extracted from the TRRUST V2.0 online database, and the TF-TG (transcription factors-target genes) network was drawn. Afterward, a list of drugs targeting TF-TG genes was obtained from the DGIdb V4.0 database, and two drug-gene interaction networks, including drug-TG and drug-TF, were drawn. After analyzing gene co-expression TF-TG, and drug-gene interaction networks, 16 drugs were selected as potent candidates for NSCLC treatment. Out of 16 selected drugs, nine drugs, namely Methotrexate, Olanzapine, Haloperidol, Fluorouracil, Nifedipine, Paclitaxel, Verapamil, Dexamethasone, and Docetaxel, were chosen from the drug-TG sub-network. In addition, nine drugs, including Cisplatin, Daunorubicin, Dexamethasone, Methotrexate, Hydrocortisone, Doxorubicin, Azacitidine, Vorinostat, and Doxorubicin Hydrochloride, were selected from the drug-TF sub-network. Methotrexate and Dexamethasone are common in drug-TG and drug-TF sub-networks. In conclusion, this study proposed 16 drugs as potent candidates for NSCLC treatment through analyzing gene co-expression, TF-TG, and drug-gene interaction networks.
肺癌是男性和女性最常见的癌症。这种癌症分为两种主要类型,即非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)。大约 85%至 90%的肺癌是非小细胞肺癌。重新定位 NSCLC 治疗中的有效候选药物是癌症研究的重要课题之一。药物重定位(DR)或药物再利用是一种识别现有药物新治疗用途的方法。本研究应用计算药物重定位方法来识别治疗 NSCLC 患者的候选药物。为此,首先从 GEO 数据库中获取 NSCLC 和健康(对照)样本的转录组学谱,其 accession number 为 GSE21933。然后,使用 WGCNA 为 NSCLC 样本重建基因共表达网络,并提取两个显著的紫色和品红色基因模块。接下来,从 TRRUST V2.0 在线数据库中提取调节紫色和品红色模块基因的转录因子基因列表,并绘制 TF-TG(转录因子-靶基因)网络。之后,从 DGIdb V4.0 数据库中获取针对 TF-TG 基因的药物列表,并绘制药物-TG 和药物-TF 两个药物-基因相互作用网络。在分析基因共表达 TF-TG 和药物-基因相互作用网络后,选择了 16 种药物作为 NSCLC 治疗的有效候选药物。在 16 种选定的药物中,有 9 种药物,即甲氨蝶呤、奥氮平、氟哌啶醇、氟尿嘧啶、硝苯地平、紫杉醇、维拉帕米、地塞米松和多西他赛,来自药物-TG 子网络。此外,还有 9 种药物,包括顺铂、柔红霉素、地塞米松、甲氨蝶呤、氢化可的松、多柔比星、阿扎胞苷、伏立诺他和盐酸多柔比星,来自药物-TF 子网络。甲氨蝶呤和地塞米松是药物-TG 和药物-TF 子网络中的常见药物。总之,本研究通过分析基因共表达、TF-TG 和药物-基因相互作用网络,提出了 16 种治疗 NSCLC 的潜在候选药物。