双硫死亡相关基因ACTN4对肺腺癌预后的影响

摘要:

目的：采用双硫死亡相关基因构建的风险评分模型在肿瘤免疫景观和预测预后方面具有出色的能力。但缺乏在肺腺癌中的研究报道。本研究探讨双硫死亡相关基因在肺腺癌中的意义及其对患者预后的影响。方法：从肿瘤与癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载正常肺和肺腺癌样本的基因表达谱及临床信息。使用Deseq2包分析差异基因，采用Cox回归分析差异基因与相关性。利用Timer数据库进行靶基因泛癌分析，按靶基因表达中位数将患者分为高表达组与低表达组，分析靶基因表达与临床特征及预后的关系。通过癌症影像档案馆(The Cancer Imaging Archive,TCIA)数据库分析靶基因和免疫相关性。最后进行临床样本免疫组织化学表达和治疗效果分析。结果：识别出预后相关的双硫死亡相关基因溶质载体家族成员SLC7A11(solute carrier family 7 member 11)、CD2AP(CD2 associated protein)和辅肌动蛋白α4(actinin alpha 4,ACTN4)，其中ACTN4的风险比最高。ACTN4在泛癌种中广泛表达，在肺腺癌中显著降低，可以显著区分不同预后的患者。ACTN4的表达与临床分期和免疫检查点表达水平显著相关。临床样本的免疫组织化学结果表明肺腺癌中ACTN4高表达患者对免疫治疗的反应效果较好。结论：双硫死亡相关基因ACTN4在肺腺癌中发挥重要作用，有望为肺腺癌患者的治疗提供一定的参考。

Abstract:

ObjectiveDisulfidpotsis-related gene risk model presents prior ability in immune landscape and prognostic prediction. However, there are few studies on lung adenocarcinoma. This study aims to investigate and screen the influence of disulfidptosis-related genes (DRGs) on the prognosis in lung adenocarcinoma and predict the response to immunotherapy.MethodsTranscriptomic and clinical data of normal and lung adenocarcinoma tissues were obtained from The Cancer Genome Atlas (TCGA). Deseq2 package and Cox regression were used to analyze differential genes and prognostic correlation, respectively. Target gene was performed by pan-caner analysis. The patients were divided into a high expression group and a low expression group according to the median expression of target gene, and then the target gene expression and clinical correlation were analyzed, prognostic relationship. The Cancer Imaging Archive (TCIA) databases were used to analyze the correlation between target genes and immunity. Finally, the immunohistochemical expression and therapeutic effect of DRGs in clinical samples were analyzed.ResultsThree DRGs, solute carrier family 7 member 11 (SLC7A11), CD2 associated protein (CD2AP), and actinin alpha 4 (ACTN4), were identified that were associated with prognosis, with ACTN4 having the highest hazard ratio. It could significantly distinguish 2 groups with different prognosis. There was a significant correlation between ACTN4 and clinical stage. In addition, ACTN4 was associated with immune checkpoints. Immunohistochemical results showed that the patients with highly ACTN4 expression had a better response to immunotherapy in lung adenocarcinoma.ConclusionDisulfidptosis-related gene ACTN4 could be a potential prognostic and therapeutic target in lung adenocarcinoma.