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基于基因表达谱探讨免疫细胞浸润对肺纤维化患者肺动脉高压发生的影响

Effect of Immune Cell Infiltration on Occurrence of Pulmonary Hypertension in Pulmonary Fibrosis Patients Based on Gene Expression Profiles.

作者信息

Zhu Feng, Zuo Lili, Hu Rui, Wang Jin, Yang Zhihua, Qi Xin, Feng Limin

机构信息

Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Department of Traditional Chinese Medicine, Hebei North University, Zhangjiakou, China.

出版信息

Front Med (Lausanne). 2021 Jul 7;8:671617. doi: 10.3389/fmed.2021.671617. eCollection 2021.

Abstract

Pulmonary hypertension (PH) is a frequent complication in patients with pulmonary fibrosis (PF), whereas the mechanism was not well-understood. This study aimed to explore the influence of immune cell infiltration on PH status based on the genomic expression profiles. Microarray data of GSE24988 were downloaded from the GEO database, including 116 lung tissue samples derived from PF patients with various PH status. Proportion of infiltrated immune cells was evaluated using CIBERSORT, a gene expression-based de-convolution algorithm. A random forest classifier was constructed and out of bag (OOB) cross-validation was carried out for PH prediction. The proportions of immune infiltration cells varied differently in PH samples except T regulatory cells (-value = 0). Compared with non-PH samples, increased number of naive B cells and plasma cells were identified in PH samples, whereas activated dendritic cells and M2 macrophages were relatively lower ( < 0.05). In the random forest model, these four types of immune cells obtained a higher variable importance score than other cells, including mean decreased accuracy and mean decreased gini evaluation. We ran the OOB cross-validation in each sample of datasets (training set and testing set) and obtained 79 and 69% accuracy, respectively. Abnormal proportions of four types of immune cells were identified in PH samples compared with non-PH samples, suggesting their involvement in PH development. In summary, the immune cell infiltration in PF patients is associated with the PH status of patients, which deserves further investigation in the future.

摘要

肺动脉高压(PH)是肺纤维化(PF)患者常见的并发症,但其机制尚不清楚。本研究旨在基于基因组表达谱探讨免疫细胞浸润对PH状态的影响。从基因表达综合数据库(GEO)下载GSE24988的微阵列数据,包括来自不同PH状态的PF患者的116份肺组织样本。使用CIBERSORT(一种基于基因表达的反卷积算法)评估浸润免疫细胞的比例。构建随机森林分类器,并对PH预测进行袋外(OOB)交叉验证。除调节性T细胞(p值=0)外,PH样本中免疫浸润细胞的比例变化不同。与非PH样本相比,PH样本中幼稚B细胞和浆细胞数量增加,而活化树突状细胞和M2巨噬细胞相对较少(p<0.05)。在随机森林模型中,这四种免疫细胞获得的变量重要性得分高于其他细胞,包括平均准确性降低和平均基尼系数评估。我们在数据集的每个样本(训练集和测试集)中进行了OOB交叉验证,准确率分别为79%和69%。与非PH样本相比,PH样本中四种免疫细胞的比例异常,表明它们参与了PH的发生发展。总之,PF患者的免疫细胞浸润与患者的PH状态相关,这值得未来进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91ae/8292720/b06ea9fd3be1/fmed-08-671617-g0001.jpg

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