Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) has high mortality worldwide. The CD247 molecule (CD247, as known as T-cell surface glycoprotein CD3 zeta chain) has been reported as a susceptibility locus in systemic sclerosis, but its correlation with IPF remains unclear.MethodsDatasets were acquired by researching the Gene Expression Omnibus (GEO). CD247 was identified as the hub gene associated with percent predicted diffusion capacity of the lung for carbon monoxide (Dlco% predicted) and prognosis according to Pearson correlation, logistic regression, and survival analysis.ResultsCD247 is significantly downregulated in patients with IPF compared with controls in both blood and lung tissue samples. Moreover, CD247 is significantly positively associated with Dlco% predicted in blood and lung tissue samples. Patients with low-expression CD247 had shorter transplant-free survival (TFS) time and more composite end-point events (CEP, death, or decline in FVC >10% over a 6-month period) compared with patients with high-expression CD247 (blood). Moreover, in the follow-up 1st, 3rd, 6th, and 12th months, low expression of CD247 was still the risk factor of CEP in the GSE93606 dataset (blood). Thirteen genes were found to interact with CD247 according to the protein–protein interaction network, and the 14 genes including CD247 were associated with the functions of T cells and natural killer (NK) cells such as PD-L1 expression and PD-1 checkpoint pathway and NK cell-mediated cytotoxicity. Furthermore, we also found that a low expression of CD247 might be associated with a lower activity of TIL (tumor-infiltrating lymphocytes), checkpoint, and cytolytic activity and a higher activity of macrophages and neutrophils.ConclusionThese results imply that CD247 may be a potential T cell-derived disease severity and prognostic biomarker for IPF.
Highlights
Idiopathic pulmonary fibrosis (IPF) causes worsening dyspnea and deteriorating lung function, which results in poor prognosis [1]
Thirteen genes were found to interact with CD247 molecule (CD247) according to the protein–protein interaction network, and the 14 genes including CD247 were associated with the functions of T cells and natural killer (NK) cells such as PD-L1 expression and PD-1 checkpoint pathway and NK cell-mediated cytotoxicity
We found that a low expression of CD247 might be associated with a lower activity of tumor-infiltrating lymphocytes (TIL), checkpoint, and cytolytic activity and a higher activity of macrophages and neutrophils
Summary
Idiopathic pulmonary fibrosis (IPF) causes worsening dyspnea and deteriorating lung function, which results in poor prognosis [1]. Increasing studies have shown that innate and adaptive immune processes can coordinate existing fibrotic responses and are associated with prognosis in patients with IPF [5, 6]. Studies have suggested that a low expression of CD247 caused in the setting of chronic inflammation was associated with decreased T cell activity [9–11]. The caused immunosuppression is only associated with downregulation of CD247 while the remaining TCR subunits are unaffected, which implies that the CD247 downregulation occurs at chronic inflammation not at acute inflammatory response [9, 10]. The CD247 molecule (CD247, as known as T-cell surface glycoprotein CD3 zeta chain) has been reported as a susceptibility locus in systemic sclerosis, but its correlation with IPF remains unclear
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