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综合鉴定血管生成相关基因预测LUAD的免疫相互作用和预后

发布者:抗性基因网 时间:2023-06-12 浏览量:319

摘要
出身背景
肿瘤微环境以血管生成为特征。肿瘤的微环境(TME)及其与免疫疗法的相互作用影响免疫疗法的有效性。在肺腺癌(LUAD)的研究中,目前多种血管生成基因与临床结果、免疫细胞浸润和免疫治疗之间没有明确的联系。
方法
从GEO和TCGA下载临床信息和相应的基因表达。对36个血管生成相关基因(ARGs)进行了综合评估,以及血管生成与转录模式和预后之间的相关性。免疫差异在亚群中表现出不同的功能和浸润。KEGG通路和GO富集分析是基于不同的聚类进行的。建立ARG_score以量化每个患者的血管生成亚型。最后,我们评估了它们在预测不同风险组的预后和治疗反应方面的价值。
后果
在遗传水平上讨论了LUAD标本中ARGs的突变。我们确定了两种不同的分子亚型,并观察到ARG突变与患者的临床特征、预后和TME有关。接下来建立预测总生存期(OS)的ARG_,
证实了其对LUAD患者的强大预测能力。此外,还创建了一个高度可靠的诺模图。低风险评分表明操作系统更好。此外,ARG核心与癌症干细胞指数和药物敏感性显著相关。FSTL3被认为是潜在的靶基因。
结论
总的来说,我们是第一个描述LUAD患者ARGs预后的人。血管生成可能在LUAD的发展中发挥重要作用。这一特征可能有助于阐明TME中血管生成的特征,并有助于探索更具成本效益的免疫治疗策略。
Abstract
Background
Tumor microenvironment is characterized by angiogenesis. A tumor's microenvironment (TME) and its interactions with immunotherapy influence
immunotherapy's effectiveness. In the study of Lung adenocarcinoma (LUAD), there is currently no clear link between multiple angiogenesis genes and clinical
results, immune cell infiltration, and immunotherapy.
Methods
Clinical information and corresponding Gene expression were downloaded from the GEO and TCGA. Thirty-six angiogenesis-related genes (ARGs) were
comprehensively evaluated, and correlations between angiogenesis and patterns of transcription and prognosis. The immune difference shows different
functions and Infiltration in the sub-cluster. KEGG pathway and GO enrichment analyses were conducted based on distinct clusters. ARG_score was
established to quantify the angiogenic subtype of each patient. Finally, we assessed their value in predicting prognosis and treatment response in the different
risk groups.
Results
The mutations of ARGs in LUAD specimens were discussed at the genetic level. We identified two distinct molecular subtypes and observed that ARG
mutations were associated with clinical characteristics, prognosis, and TME of patients. Next, an ARG_score predicting overall survival (OS) was established,
confirming its robust predictive power for patients with LUAD. Moreover, a highly reliable Nomogram was created. Low risk score demonstrated better OS. In
addition, the ARG_score was shown to be significantly correlated with cancer stem cell index and drug sensitivity. FSTL3 is considered potential target gene.
Conclusion
In general, we were the first to characterize the prognosis of ARGs in patients with LUAD. Angiogenesis may play an essential role in the development of LUAD.
This characterization may assist in clarifying the features of angiogenesis in TME and enable the exploration of more cost-effective immunotherapy
strategies.


https://assets.researchsquare.com/files/rs-2417491/v1/e46c64c7-e54f-42cc-a5a5-c3579c7887e7.pdf?c=1673036461