非小细胞肺癌干细胞靶点筛选及NDC80临床意义分析

doi:10.20223/j.cnki.1000-8535.2025.12.004

摘要/Abstract

摘要： 目的通过生物信息学手段筛选非小细胞肺癌（NSCLC）中的关键靶点基因,识别预后标志物NDC80,并探讨其在NSCLC中的表达意义,进而分析NDC80作为NSCLC基因治疗靶点的可行性。方法采用癌症基因组图谱（TCGA）TCGA数据库检索NSCLC相关数据,进行加权基因共表达网络分析（WGCNA）以识别关键基因,并进行差异表达分析、相关性分析和蛋白互作网络构建。对筛选出的关键基因进行功能分析。利用免疫组化染色法检测癌组织及癌旁组织中NDC80蛋白的表达水平,并进一步探究其与临床病理特征的关系。采用Kaplan-Meier法分析NDC80表达与NSCLC患者无进展生存时间（PFS）的关系。结果共筛选出20个与NSCLC高度关联的关键基因,包括CDC20、CDK1、MCM4、CDC6、MCM2、PLK1、NDC80、CCNB1、CDC45、AURKA、MCM8、BUB1、CDT1、ORC1、CCNA2、CASC5、MAD2L1、BUB1B、CENPA、AURKB。免疫组化验证显示,NDC80蛋白在NSCLC组织中高表达,其在NSCLC组（阳性表达率88.6%）显著高于癌旁组（50.0%）（P<0.05）。NDC80蛋白的阳性表达率在TNM分期（Ⅲ期+Ⅳ期）、低分化、淋巴结转移的NSCLC组高于TNM分期（Ⅰ期+Ⅱ期）、高分化及中分化以及未发生淋巴结转移的NSCLC组（P<0.05）。NDC80蛋白的阳性表达率在不同性别、年龄、病灶大小分类的NSCLC组织中无显著差异（P>0.05）。Kaplan-Meier分析显示,NDC80蛋白高表达组的PFS中位数为（9.00±0.27）个月,明显低于低表达组（11.00±0.79）个月（P<0.05）。结论本研究发现的关键基因在NSCLC干细胞的维持中发挥重要作用。免疫组化结果显示,NDC80蛋白在NSCLC组织中高表达,且与肿瘤分化、TNM分期及淋巴结转移密切相关。NDC80蛋白高表达组的PFS明显低于低表达组,提示NDC80可能成为NSCLC筛查、治疗和预后评估的潜在生物标志物。

关键词: 非小细胞肺癌, 肿瘤干细胞, NDC80, 生物信息学, 靶向治疗

Abstract: Objective To screen the key target genes in non-small cell lung cancer（NSCLC）by bioinformatics,identify the prognostic marker NDC80,and explore its expression significance in NSCLC,so as to analyze the feasibility of NDC80 as a gene therapy target for NSCLC．Methods TCGA database was used to retrieve NSCLC-related data,and weighted gene co-expression network analysis（WGCNA）was used to identify key genes,and differential expression analysis,correlation analysis and protein-protein interaction network construction were carried out．The function of the selected key genes was analyzed．Immunohistochemical staining was used to detect the expression level of NDC80 protein in cancer tissues and adjacent tissues,and to further explore its relationship with clinicopathological features．Kaplan-Meier method was used to analyze the relationship between NDC80 expression and progression-free survival （PFS）of NSCLC patients．Results A total of 20 key genes highly associated with NSCLC were screened out,which were CDC20,CDK1,MCM4,CDC6,MCM2,PLK1,NDC80,CCNB1,CDC45,AURKA,MCM8,BUB1,CDT1,ORC1,CCNA2,CASC5,MAD2L1,BUB1B and CENPA．Immunohistochemical verification showed that NDC80 protein was highly expressed in NSCLC tissue,and its positive expression rate in NSCLC group（88.6%）was significantly higher than that in adjacent cancer group（50.0%,P<0.05）．The positive expression rate of NDC80 protein in NSCLC with TNM staging（Ⅲ+Ⅳ）,low differentiation and lymph node metastasis was higher than that in NSCLC with TNM staging（Ⅰ+Ⅱ）,high differentiation and moderate differentiation and no lymph node metastasis（P<0.05）．There was no significant difference in the positive expression rate of NDC80 protein among NSCLC tissues with different gender,age and lesion size（P>0.05）．Kaplan-Meier analysis showed that the median PFS of high expression group of NDC80 protein was（9.00±0.27）months,which was significantly lower than that of low expression group（11.00±0.79）months（P<0.05）．Conclusions The key genes found in this study play an important role in the maintenance of NSCLC stem cells．Immunohistochemical results showed that NDC80 protein was highly expressed in NSCLC,and it was closely related to tumor differentiation,TNM staging and lymph node metastasis．The PFS of high expression group of NDC80 protein was significantly lower than that of low expression group,suggesting that NDC80 may become a potential biomarker for screening,treatment and prognosis evaluation of NSCLC．

Key words: non-small cell lung cancer, cancer stem cells, NDC80, bioinformatics, targeted therapy

范丽丽, 常金. 非小细胞肺癌干细胞靶点筛选及NDC80临床意义分析[J]. 广州医药, 2025, 56(12): 1638-1650.

FAN Lili, CHANG Jin. Screening of stem cell targets for non-small cell lung cancer and analysis of clinical significance of NDC80[J]. Guangzhou Medical Journal, 2025, 56(12): 1638-1650.

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