首页|基于生物信息学探究GJB3与肺癌转移的关系及其临床意义

基于生物信息学探究GJB3与肺癌转移的关系及其临床意义

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目的:探索与上皮-间质转化相关的新的预后标志物和治疗靶点.方法:从TCGA数据库获取肺腺癌(LUAD)患者的体细胞突变数据、甲基化数据、基因表达谱及对应的临床信息,通过ssGSEA算法对TCGA患者进行上皮-间质转化相关功能的评分,对高评分患者与低评分患者进行差异分析,筛选出GJB3这一基因.研究GJB3对上皮-间质转化、肺腺癌患者预后、DNA甲基化、基因组不稳定性、免疫浸润、免疫治疗及化疗响应等功能的影响,最后使用GEO数据库验证GJB3与肺腺癌患者预后之间的关联.结果:GJB3与上皮-间质转化显著相关.GJB3的高表达预示着LUAD患者较差的总生存期(OS)、无进展间期(PFI)和疾病特异性生存期(DSS).Cox回归分析表明,GJB3是影响LUAD患者OS的独立生物标志物.此外,使用其他三个LUAD数据集验证GJB3在LUAD中的预后作用,得到了相似的结果.Meta分析表明,GJB3的高表达与较差的OS密切相关.高表达的GJB3与基因组不稳定性增加、免疫治疗和化疗响应不佳相关.肺癌患者单细胞数据分析结果表明,GJB3主要在肺癌细胞上表达.结论:GJB3在肺腺癌中高表达,促进肺腺癌的进展.其有望作为独立预测肺腺癌预后的生物标志物,为理解和探索肺腺癌的早期诊断和临床治疗提供线索.
Exploring the relationship between GJB3 and lung cancer metastasis and its clinical significance based on bioinformatics analysis
Objective:To explore new prognostic markers and therapeutic targets associated with epithelial-mesenchymal transition.Methods:Somatic mutation data,methylation data,gene expres-sion profiles,and corresponding clinical information of lung adenocarcinoma(LUAD)patients were obtained from the cancer genome atlas(TCGA)database.We scored the functions related to the epithelial-mesenchymal transition of TCGA patients by the ssGSEA algorithm and analyzed the differences between high-scoring patients and low-scoring patients,therefore screening out the gene GJB3.Next,we examined GJB3's role in the epithelial-mesenchymal transition,lung adenocarcino-ma patient prognosis,DNA methylation,genomic instability,immune infiltration,immunotherapy,and chemotherapy response,and finally verified the association between GJB3 and prognosis of LUAD patients in the GEO database.Results:GJB3 was significantly associated with epithelial-mesenchymal transition.High expression of GJB3 predicted poor overall survival(OS),progress-free interval(PFI),and disease-specific survival(DSS)in LUAD patients.Cox regression analysis showed that GJB3 was an independent biomarker of OS in LUAD patients.In addition,we used three other LUAD datasets to validate the prognostic role of GJB3 in LUAD and obtained simi-lar results.Meta-analysis showed that high GJB3 expression was strongly associated with poor OS.Conclusion:GJB3 is highly expressed in LUAD and promotes its progression.GJB3 may serve as an independent biomarker for predicting the prognosis of lung adenocarcinoma and providing clues for early diagnosis and clinical treatment.

Lung AdenocarcinomaEpithelial-Mesenchymal TransitionPrognostic Signa-tureBioinformaticsGenome Instability

戴玮婧、李杨仪、张建国、李思琦、白睿、姬倩、何发键、欧阳雯、唐芳、王志浩、谢丛华

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武汉大学中南医院肺部肿瘤科

肿瘤生物学行为湖北省重点实验室

湖北省肿瘤临床研究中心 湖北 武汉 430071

肺腺癌 上皮-间质转化 预后标志物 生物信息学 基因组不稳定性

2024

武汉大学学报(医学版)
武汉大学

武汉大学学报(医学版)

CSTPCD
影响因子:0.959
ISSN:1671-8852
年,卷(期):2024.45(11)