Department of Oncology, Pingxiang Second People's Hospital, Pingxiang, Jiangxi 337000, China.
Department of Oncology, Gaoxin Hospital of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330096, China.
Biomed Res Int. 2022 Nov 28;2022:5956526. doi: 10.1155/2022/5956526. eCollection 2022.
Lung squamous cell carcinoma (LUSC) has poor survival prognosis and few clinical treatment options. We urgently need to explore new therapeutic drugs in clinical practice. Cepharanthine (CEP) has been shown to have anticancer effects in several tumors, but the mechanism of CEP in treating LUSC has not been reported.
SwissTargetPrediction, PharmMapper, and GeneCards were used to identify targets of CEP and LUSC. Further topological analysis was used to obtain hub genes via Cytoscape. Molecular docking was carried out to verify the combination of CEP with hub targets. Based on bioinformatics, we first analyzed the expression and survival of hub targets in LUSC and further analyzed the correlation between hub targets and cancer stemness, immune cell infiltration, and tumor mutation burden (TMB).
A total of 41 targets were identified. Further topological analysis identified 6 hub genes: AURKA, CCNA2, CCNE1, CDK1, CHEK1, and PLK1. Molecular docking analysis showed that CEP had stable binding to all these 6 target proteins. In-depth bioinformatics analysis of these 6 targets showed that high expression of these targets were positively correlated with cancer stemness index and negatively correlated with tumor infiltrating immune cells. In immune subtype analysis, the expressions of these targets were significantly decreased in inflammatory tumors. In addition, we also found that the expressions of these targets were positively correlated with TMB.
Based on multidisciplinary analysis, we preliminarily identified potential targets of CEP for LUSC treatment and suggested that CEP may play a role in regulating LUSC stemness.
肺鳞状细胞癌（LUSC）的预后较差，临床治疗选择有限。我们迫切需要在临床实践中探索新的治疗药物。水黄皮素（CEP）已在多种肿瘤中显示出抗癌作用，但 CEP 治疗 LUSC 的机制尚未报道。
使用 SwissTargetPrediction、PharmMapper 和 GeneCards 鉴定 CEP 和 LUSC 的靶点。进一步通过 Cytoscape 进行拓扑分析以获得枢纽基因。进行分子对接以验证 CEP 与枢纽靶标的结合。基于生物信息学，我们首先分析了 LUSC 中枢纽靶标的表达和生存情况，并进一步分析了枢纽靶标与癌症干性、免疫细胞浸润和肿瘤突变负担（TMB）之间的相关性。
共鉴定出 41 个靶点。进一步的拓扑分析确定了 6 个枢纽基因：AURKA、CCNA2、CCNE1、CDK1、CHEK1 和 PLK1。分子对接分析表明 CEP 与这 6 个靶蛋白均具有稳定的结合。对这 6 个靶标的深入生物信息学分析表明，这些靶标的高表达与癌症干性指数呈正相关，与肿瘤浸润免疫细胞呈负相关。在免疫亚型分析中，这些靶标的表达在炎症性肿瘤中显著降低。此外，我们还发现这些靶标的表达与 TMB 呈正相关。
通过多学科分析，我们初步鉴定了 CEP 治疗 LUSC 的潜在靶点，并提出 CEP 可能在调节 LUSC 干性方面发挥作用。
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