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生物信息学分析鉴定急性肺损伤中的免疫浸润和有效免疫生物标志物。

Identification of Immune Infiltration and Effective Immune Biomarkers in Acute Lung Injury by Bioinformatics Analysis.

机构信息

Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.

出版信息

Cell Transplant. 2022 Jan-Dec;31:9636897221124485. doi: 10.1177/09636897221124485.

Abstract

Acute lung injury (ALI) is a serious complication in clinical settings. This study aimed to elucidate the immune molecular mechanisms underlying ALI by bioinformatics analysis. Human ALI and six ALI mouse model datasets were collected. Immune cell infiltration between the ALI samples and non-ALI controls was estimated using the ssGSEA algorithm. Least absolute shrinkage and selection operator (LASSO) regression analysis and Wilcoxon test were performed to obtain the significantly different immune cell infiltration types. Immune feature genes were screened by differential analysis and the weighted correlation network analysis (WGCNA) algorithm. Functional enrichment was then performed and candidate hub biomarkers were identified. Finally, the receiver operator characteristic curve (ROC) analysis was used to predict their diagnostic performances. Three significantly different immune cell types (B cells, CD4 T cells, and CD8 T cells) were identified between the ALI samples and controls. A total of 13 immune feature genes were obtained by WGCNA and differential analysis and found to be significantly associated with immune functions and lung diseases. Four hub genes, including CD180, CD4, CD74, and MCL1 were identified using cytoHubba and were shown to have good specificity and sensitivity for the diagnosis of ALI. Correlation analysis suggested that CD4 was positively associated with T cells, whereas MCL1 was negatively correlated with B and T cells. We found that CD180, CD4, CD74, and MCL1 can serve as specific immune biomarkers for ALI. MCL1-B cell, MCL1-T cell, and CD4-T cell axes may be involved in the progression of ALI.

摘要

急性肺损伤 (ALI) 是临床中的一种严重并发症。本研究旨在通过生物信息学分析阐明 ALI 的免疫分子机制。收集了人类 ALI 和六个 ALI 小鼠模型数据集。使用 ssGSEA 算法估计 ALI 样本与非 ALI 对照之间的免疫细胞浸润情况。通过最小绝对收缩和选择算子 (LASSO) 回归分析和 Wilcoxon 检验获得差异浸润的免疫细胞类型。通过差异分析和加权相关网络分析 (WGCNA) 算法筛选免疫特征基因。然后进行功能富集并鉴定候选枢纽生物标志物。最后,使用接收器操作特征曲线 (ROC) 分析预测其诊断性能。在 ALI 样本和对照组之间鉴定出三种明显不同的免疫细胞类型 (B 细胞、CD4 T 细胞和 CD8 T 细胞)。通过 WGCNA 和差异分析共获得 13 个免疫特征基因,发现它们与免疫功能和肺部疾病显著相关。使用 cytoHubba 鉴定出 4 个枢纽基因,包括 CD180、CD4、CD74 和 MCL1,它们对 ALI 的诊断具有良好的特异性和敏感性。相关性分析表明 CD4 与 T 细胞呈正相关,而 MCL1 与 B 和 T 细胞呈负相关。我们发现 CD180、CD4、CD74 和 MCL1 可作为 ALI 的特异性免疫生物标志物。MCL1-B 细胞、MCL1-T 细胞和 CD4-T 细胞轴可能参与 ALI 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06d0/9523839/d8413e64ab87/10.1177_09636897221124485-fig1.jpg

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