ObjectiveThe study aims to identify potential diagnostic markers of idiopathic pulmonary fibrosis (IPF) and analyze the significance of immune cell infiltration in this pathology.Materials and methodsDownload two publicly available gene expression profiles (GSE10667 and GSE24206 datasets) from the GEO database including 48 Idiopathic pulmonary fibrosis (IPF) samples and 21 human control samples and select for distinctly expressed genes (DEG) from them. Lasso regression model and support vector machine recursive feature elimination S,V,R,F analysis were used to check candidate biomarkers. The area under the subject’s work characteristic curve (AUC) value is used to evaluate its recognition ability. The GSE53845 dataset (40 IPF patients and 8 controls) continue to validate the expression level and diagnostic value of biomarkers in IPF. Comprehensive analysis of immune infiltrated cells of IPF was performed using R software and immune cell infiltration estimation analysis tool- deconvolution algorithm (CIBERSORT).Results43 DEGs were identified in total. The identified DEGs mostly involve pneumonia, lung disease, collagen disease, obstructive pulmonary disease and other diseases. The activation of IL-17 signaling pathways, amoebic disease, interaction of viral proteins with cytokines and cytokine receptors, protein digestion and absorption, and flaccid hormone signaling pathways in IPF were different from the control group. The expression degree of CRTAC1, COL10A1, COMP, RPS4Y1, IGFL2, NECAB1, SCG5, SLC6A4, and SPP1 in IPF tissue were prominently higher than the normal group. Immune cell infiltration analysis showed that CRTAC1, COL10A1, COMP, IGFL2, NECAB1, SCG5, SLC6A4, and SPP1 were associated with monocytes, plasma cells, neutrophils, and regulatory (treg) T cells.ConclusionCRTAC1, COL10A1, COMP, IGFL2, NECAB1, SCG5, SLC6A4, and SPP1 can be used as diagnostic markers for IPF, providing new ideas for the future study of IPF occurrence and molecular mechanisms.

By evaluating S100 calcium binding protein A9 (S100A9) and Klebs von den Lungen-6 (KL-6) expression in patients with 4 common interstitial lung diseases (ILDs), we aimed to investigate whether S100A9 or KL-6 can be of any value in the differential diagnosis of these ILDs and simultaneously signal the disease progression. We collected the data of patients diagnosed with the 4 ILDs and underwent fiber-optic bronchoscopy and BAL in the First Affiliated Hospital, China Medical University from January 2012 to December 2020. The data related to BGA, C-reactive protein, pulmonary function test, total number and fraction of cells, T lymphocyte subsets in bronchoalveolar lavage fluid (BALF), and the expression of S100A9 and KL-6 in BALF and serum were collected. We analyzed, whether S100A9 or KL-6 could serve as a biomarker for differential diagnosis between the 4 common ILDs; whether the levels of S100A9 and KL-6 correlated with each other; whether they were correlated with other clinical parameters and disease severity. This study included 98 patients, 37 patients with idiopathic pulmonary fibrosis (IPF), 12 with hypersensitivity pneumonitis, 13 with connective tissue disease-associated ILD, and 36 with sarcoidosis (SAR): stage I (18), stage II (9), stage III (5), and stage IV (4). The expression of KL-6 in BALF was significantly higher in IPF patients than other 3 groups (all P -value < .05). However, there was no significant difference in the levels of S100A9 in BALF and serum between the 4 groups ( P -value > .05). The levels of S100A9 in BALF of IPF patients was positively and significantly correlated with KL-6 expression and the percentage of neutrophils in BALF ( P -value < .05). Along with the stage increase of SAR patients, the level of S100A9 in BALF gradually increased, which was negatively and significantly correlated with the forced vital capacity/predicted, carbon monoxide diffusing capacity/predicted%, and PaO 2 (all P -value < .05). The expression of KL-6 in BALF can be used as a biomarker to differentiate IPF from the other 3 common ILDs. While, this was not the case with expression of S100A9 in BALF and serum. However, the expression S100A9 in BALF is useful to indicate the progression of SAR. Thus, simultaneous measurement of KL-6 and S100A9 levels in BALF makes more sense in differential diagnosing of the 4 common ILDS.