非小细胞肺癌的新预后生物标记及治疗靶点的识别与验证。
Identification and validation of novel prognostic biomarkers and therapeutic targets for non-small cell lung cancer.
发表日期:2023
作者:
Li-Ting Lai, Yuan-Hui Ren, Ya-Jun Huai, Yu Liu, Ying Liu, Shan-Shan Wang, Jin-Hong Mei
来源:
Frontiers in Genetics
摘要:
背景:虽然抗PD-1/PD-L1免疫疗法具有显著的生存益处,但非小细胞肺癌(NSCLC)仍然是全球最常见的肿瘤和癌症相关死亡的主要原因之一。因此,急需确定该难治性疾病的新治疗靶点。方法:本研究通过Venn图集成了微阵列数据集GSE27262,GSE75037,GSE102287和GSE21933。我们使用R进行功能聚类和通路富集分析。通过STRING数据库和Cytoscape,我们进行了蛋白质相互作用(PPI)网络分析,并确定了关键基因,这些基因通过GEPIA2和UALCAN门户网站进行了验证。通过定量实时聚合酶链式反应和Western blotting验证了肌动蛋白结合蛋白anillin(ANLN)。此外,使用Kaplan-Meier方法计算了存活分析。结果:共鉴定了126个差异表达基因,这些基因富集于有丝分裂核分裂、有丝分裂细胞周期G2/M转换、血管生成、纺锤体和过氧化物酶激活受体信号通路。在PPI网络复合物中鉴定了12个中心节点基因。存活分析显示,高转录水平与NSCLC患者劣质生存相关。进一步探讨了ANLN的临床意义;其蛋白表达呈逐渐增加的趋势,从一级到三级。结论:这些重要基因可能参与NSCLC的癌变和进展,可能为NSCLC的诊断和治疗提供有用的靶点。Copyright © 2023 Lai,Ren,Huai,Liu,Liu,Wang和Mei。
Background: Despite the significant survival benefits of anti-PD-1/PD-L1 immunotherapy, non-small cell lung cancer (NSCLC) remains one of the most common tumors and major causes of cancer-related deaths worldwide. Thus, there is an urgent need to identify new therapeutic targets for this refractory disease. Methods: In this study, microarray datasets GSE27262, GSE75037, GSE102287, and GSE21933 were integrated by Venn diagram. We performed functional clustering and pathway enrichment analyses using R. Through the STRING database and Cytoscape, we conducted protein-protein interaction (PPI) network analysis and identified the key genes, which were verified by the GEPIA2 and UALCAN portal. Validation of actin-binding protein anillin (ANLN) was performed by quantitative real-time polymerase chain reaction and Western blotting. Additionally, Kaplan-Meier methods were used to compute the survival analyses. Results: In total, 126 differentially expressed genes were identified, which were enriched in mitotic nuclear division, mitotic cell cycle G2/M transition, vasculogenesis, spindle, and peroxisome proliferator-activated receptor signaling pathway. 12 central node genes were identified in the PPI network complex. The survival analysis revealed that high transcriptional levels were associated with inferior survival in NSCLC patients. The clinical implication of ANLN was further explored; its protein expression showed a gradually increasing trend from grade I to III. Conclusion: These Key genes may be involved in the carcinogenesis and progression of NSCLC, which may serve as useful targets for NSCLC diagnosis and treatment.Copyright © 2023 Lai, Ren, Huai, Liu, Liu, Wang and Mei.