CX3CR1 相关免疫浸润基因联合模型评估特发性肺纤维化的预后。
The Combined Model of CX3CR1-Related Immune Infiltration Genes to Evaluate the Prognosis of Idiopathic Pulmonary Fibrosis.
机构信息
Transplantation Center, The 3rd Xiangya Hospital, Central South University, Changsha, China.
Department of Spine Surgery, The 3rd Xiangya Hospital, Central South University, Changsha, China.
出版信息
Front Immunol. 2022 Feb 10;13:837188. doi: 10.3389/fimmu.2022.837188. eCollection 2022.
BACKGROUND
High expression of chemokine (C-X3-C motif) receptor 1 (CX3CR1) was shown to contribute to the progression of many fibrotic diseases. However, there is still no study for the role of CX3CR1 in idiopathic pulmonary fibrosis (IPF). Therefore, we aimed to identify CX3CR1-related immune infiltration genes (IIGs) in IPF and establish a combined risk model to evaluate the prognosis of IPF.
METHODS
A discovery cohort of IPF patients (GSE70867) was downloaded from the Gene Expression Omnibus dataset. We identified the composition of 22 kinds of immune cells infiltration by CIBERSORT. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing CX3CR1-related IIGs. Kaplan-Meier was applied to plot the survival curve of prognosis model. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by quantitative reverse transcriptase-PCR (qRT-PCR) from 15 clinical samples, including 8 healthy controls (HC), 4 patients with usual interstitial pneumonia (UIP) and 3 patients with pulmonary fibrosis (FIB).
RESULTS
We found that high expression of CX3CR1 in BALF contributed to the poor prognosis in IPF patients. ALR4C, RAB37, GPR56, MARCKS, PXN and RASSF2 were identified as CX3CR1-related IIGs, which were highly expressed in PBMC of UIP/FIB patients than that of HC. Moreover, the expression of PXN was higher in FIB patients' PBMC than that of UIP ones. In the cohort of IPF patients, high infiltration of activated NK cells in BALF caused poor survival compared to low infiltration group. The infiltration of activated NK was regulated by CX3CR1-related IIGs. The combined risk model predicted that high expression of CX3CR1-related IIGs and high infiltrated activated NK cells caused poor prognosis in IPF patients.
CONCLUSION
We identified a group of CX3CR1-related IIGs in IPF patients. This combined risk model provided new insights in the prognosis and therapy of IPF.
背景
趋化因子(C-X3-C 基序)受体 1(CX3CR1)的高表达被证明有助于许多纤维化疾病的进展。然而，目前还没有关于 CX3CR1 在特发性肺纤维化(IPF)中的作用的研究。因此，我们旨在确定 IPF 中与 CX3CR1 相关的免疫浸润基因(IIGs)，并建立一个联合风险模型来评估 IPF 的预后。
方法
从基因表达综合数据库中下载 IPF 患者的发现队列(GSE70867)。我们通过 CIBERSORT 鉴定了 22 种免疫细胞浸润的组成。采用 Cox 回归模型与 LASSO 方法鉴定预后基因，并建立 CX3CR1 相关的 IIGs。Kaplan-Meier 用于绘制预后模型的生存曲线。从 15 个临床样本中收集外周血单核细胞(PBMC)和支气管肺泡灌洗液(BALF)，包括 8 个健康对照(HC)、4 个特发性间质性肺炎(UIP)患者和 3 个肺纤维化(FIB)患者。
结果
我们发现 BALF 中 CX3CR1 的高表达与 IPF 患者的不良预后有关。ALR4C、RAB37、GPR56、MARCKS、PXN 和 RASSF2 被鉴定为 CX3CR1 相关的 IIGs，在 UIP/FIB 患者的 PBMC 中表达高于 HC。此外，FIB 患者的 PBMC 中 PXN 的表达高于 UIP 患者。在 IPF 患者队列中，BALF 中活化 NK 细胞的高浸润与低浸润组相比，生存情况较差。活化 NK 的浸润受 CX3CR1 相关 IIGs 的调节。联合风险模型预测，CX3CR1 相关 IIGs 的高表达和活化 NK 细胞的高浸润导致 IPF 患者预后不良。
结论
我们在 IPF 患者中鉴定了一组 CX3CR1 相关的 IIGs。该联合风险模型为 IPF 的预后和治疗提供了新的见解。
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