A prognostic model of lung adenocarcinoma constructed based on circadian rhythm genes and its potential clinical significance.

IF 3.5 3区 医学 Q2 ONCOLOGY Frontiers in Oncology Pub Date : 2025-02-18 eCollection Date: 2025-01-01 DOI:10.3389/fonc.2025.1464578
Cong Fu, Lin Sun, Cuncheng Feng, Tong Zhou, Yanzhi Bi
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Abstract

Background: Lung adenocarcinoma (LUAD) is a common pathological category of lung cancer. Circadian rhythm (CR) disruption has been demonstrated to impact on lung tumorigenesis in mouse models. The aim of this study was to mine genes relevant to CR in LUAD and construct a corresponding risk model.

Methods: CRRGs from GSEA-MsigDB were filtered by overlapping DEGs in LUAD and NC specimens, two clusters with survival and clinical discrepancies, and CRRGs. Cox regression analysis (univariate and multivariate) was used to establish a CR-relevant risk model, which was validated in both the training and validation sets. Differences in immune infiltration, immunotherapy, and drug sensitivity between subgroups were explored. Prognostic gene expression was tested in clinical cancer and paracancer tissue samples using RT-qPCR.

Results: A grand total of two prognostic genes (CDK1 and HLA-DMA) related to CR were screened. The AUC values of a CR-relevant risk model in predicting 1/3/5-years survival in LUAD patients were greater than 0.6, indicating that the efficiency of the model was decent. Then, the results of CIBERSORT demonstrated noticeable differences in the tumor microenvironment between CR-relevant high- and low-risk subgroups. In addition, the CR-relevant risk score could be performed to estimate the effectiveness of immunotherapy in LUAD patients. The sensitivity of three common drugs (homoharringtonine, lapatinib, and palbociclib) in LUAD could be evaluated by the CR-relevant risk model. Ultimately, the experimental results confirmed that the expression trends of CDK1 and HLA-DMA in our collected clinical samples were in line with the expression trends in the TCGA-LUAD dataset.

Conclusion: In conclusion, a CR-relevant risk model based on CDK1 and HLA-DMA was constructed by using bioinformatics analysis, which might supply a new insight into the improved prognosis of LUAD.

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基于昼夜节律基因的肺腺癌预后模型及其潜在临床意义。
背景:肺腺癌(LUAD)是一种常见的肺癌病理类型。在小鼠模型中,昼夜节律(CR)中断已被证明对肺肿瘤发生有影响。本研究旨在挖掘LUAD中与CR相关的基因,并构建相应的风险模型。方法:对GSEA-MsigDB中的CRRGs进行筛选,筛选LUAD和NC标本中存在生存和临床差异的两个聚类的重叠deg,以及CRRGs。采用Cox回归分析(单因素和多因素)建立cr相关风险模型,并在训练集和验证集进行验证。观察各组间免疫浸润、免疫治疗及药物敏感性的差异。应用RT-qPCR检测临床肿瘤和癌旁组织样本中的预后基因表达。结果:共筛选了两种与CR相关的预后基因(CDK1和HLA-DMA)。cr相关风险模型预测LUAD患者1/3/5年生存率的AUC值大于0.6,表明该模型的有效性较好。然后,CIBERSORT的结果显示,在cr相关的高危亚组和低危亚组之间,肿瘤微环境存在显著差异。此外,cr相关风险评分可用于评估LUAD患者免疫治疗的有效性。采用cr相关风险模型评价三种常用药物(homoharingtonine, lapatinib, palbociclib)在LUAD中的敏感性。最终,实验结果证实了我们收集的临床样本中CDK1和HLA-DMA的表达趋势与TCGA-LUAD数据集中的表达趋势一致。结论:通过生物信息学分析,构建了基于CDK1和HLA-DMA的cr相关风险模型,为改善LUAD预后提供了新的思路。
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来源期刊
Frontiers in Oncology
Frontiers in Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
6.20
自引率
10.60%
发文量
6641
审稿时长
14 weeks
期刊介绍: Cancer Imaging and Diagnosis is dedicated to the publication of results from clinical and research studies applied to cancer diagnosis and treatment. The section aims to publish studies from the entire field of cancer imaging: results from routine use of clinical imaging in both radiology and nuclear medicine, results from clinical trials, experimental molecular imaging in humans and small animals, research on new contrast agents in CT, MRI, ultrasound, publication of new technical applications and processing algorithms to improve the standardization of quantitative imaging and image guided interventions for the diagnosis and treatment of cancer.
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