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一种基于与上皮-间质转化相关分子簇的特发性肺纤维化预后模型。

A prognostic model based on clusters of molecules related to epithelial-mesenchymal transition for idiopathic pulmonary fibrosis.

作者信息

Zhao Jiarui, Wang Can, Fan Rui, Liu Xiangyang, Zhang Wei

机构信息

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Front Genet. 2023 Jan 6;13:1109903. doi: 10.3389/fgene.2022.1109903. eCollection 2022.

Abstract

Most patients with idiopathic pulmonary fibrosis (IPF) have poor prognosis; Effective predictive models for these patients are currently lacking. Epithelial-mesenchymal transition (EMT) often occurs during idiopathic pulmonary fibrosis development, and is closely related to multiple pathways and biological processes. It is thus necessary for clinicians to find prognostic biomarkers with high accuracy and specificity from the perspective of Epithelial-mesenchymal transition. Data were obtained from the Gene Expression Omnibus database. Using consensus clustering, patients were grouped based on Epithelial-mesenchymal transition-related genes. Next, functional enrichment analysis was performed on the results of consensus clustering using gene set variation analysis. The gene modules associated with Epithelial-mesenchymal transition were obtained through weighted gene co-expression network analysis. Prognosis-related genes were screened least absolute shrinkage and selection operator (LASSO) regression analysis. The model was then evaluated and validated using survival analysis and time-dependent receiver operating characteristic (ROC) analysis. A total of 239 Epithelial-mesenchymal transition-related genes were obtained from patients with idiopathic pulmonary fibrosis. Six genes with strong prognostic associations (C-X-C chemokine receptor type 7 [], heparan sulfate-glucosamine 3-sulfotransferase 1 [], matrix metallopeptidase 25 [], murine retrovirus integration site 1 [], transmembrane four L6 family member 1 [], and tyrosylprotein sulfotransferase 1 []) were identified least absolute shrinkage and selection operator and Cox regression analyses. A prognostic model was then constructed based on the selected genes. Survival analysis showed that patients with high-risk scores had worse prognosis based on the training set [hazard ratio (HR) = 7.31, < .001] and validation set (HR = 2.85, = .017). The time-dependent receiver operating characteristic analysis showed that the area under the curve (AUC) values in the training set were .872, .905, and .868 for 1-, 2-, and 3-year overall survival rates, respectively. Moreover, the area under the curve values in the validation set were .814, .814, and .808 for 1-, 2-, and 3-year overall survival rates, respectively. The independent prognostic model constructed from six Epithelial-mesenchymal transition-related genes provides bioinformatics guidance to identify additional prognostic markers for idiopathic pulmonary fibrosis in the future.

摘要

大多数特发性肺纤维化(IPF)患者预后较差;目前缺乏针对这些患者的有效预测模型。上皮-间质转化(EMT)在特发性肺纤维化发展过程中经常发生,并且与多种途径和生物学过程密切相关。因此,临床医生有必要从上皮-间质转化的角度寻找具有高准确性和特异性的预后生物标志物。数据来自基因表达综合数据库。使用一致性聚类,根据上皮-间质转化相关基因对患者进行分组。接下来,使用基因集变异分析对一致性聚类结果进行功能富集分析。通过加权基因共表达网络分析获得与上皮-间质转化相关的基因模块。通过最小绝对收缩和选择算子(LASSO)回归分析筛选预后相关基因。然后使用生存分析和时间依赖性受试者工作特征(ROC)分析对模型进行评估和验证。从特发性肺纤维化患者中总共获得了239个上皮-间质转化相关基因。通过最小绝对收缩和选择算子及Cox回归分析,鉴定出六个具有强预后关联的基因(C-X-C趋化因子受体7型[]、硫酸乙酰肝素-葡糖胺3-磺基转移酶1[]、基质金属肽酶25[]、鼠逆转录病毒整合位点1[]、跨膜四区超家族成员1[]和酪氨酰蛋白磺基转移酶1[])。然后基于所选基因构建了一个预后模型。生存分析表明,根据训练集[风险比(HR)=7.31,<.001]和验证集(HR = 2.85,=.017),高风险评分的患者预后较差。时间依赖性受试者工作特征分析表明,训练集中1年、2年和3年总生存率的曲线下面积(AUC)值分别为.872、.905和.868。此外,验证集中1年、2年和3年总生存率的曲线下面积值分别为.814、.814和.808。由六个上皮-间质转化相关基因构建的独立预后模型为未来识别特发性肺纤维化的其他预后标志物提供了生物信息学指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fad2/9853015/d1a8ebc5f4cd/fgene-13-1109903-g001.jpg

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