To obtain the differential genes of primary Sjögren's syndrome (pSS) -idiopathic pulmonary fibrosis (IPF) and related pathways by bioinformatics methods, and to match and predict the potential Chinese medicines for treating pSS-IPF.

The gene chip data of training data set and validation data set were downloaded from GEO database, and the interaction networks of differential genes and proteins in pSS-IPF samples were determined. The key genes were identified by CytoHubba plug-in, and the disease-related functional modules were clustered and analyzed by MCODE plug-in. The transcription factors of common differentially expressed genes were predicted by TRRUST database. The GO function and KEGG pathway of key genes were analyzed to clarify the biological process of key genes. At the same time, the results of the previous analysis were verified by the differential gene expression in the verification set. Finally, the Coremine Medical database was used to predict the traditional Chinese medicine with significant regulatory effect on key genes.

A total of 136 differentially expressed genes of pSS-IPF were obtained from GEO database, and 127 nodes and 474 edge groups were obtained by importing them into STRING database. The MCODE plug-in performs cluster analysis on the PPI network and mines five disease-related functional modules. The CytoHubba plug-in searched 25 Hub genes in the relational network data and uploaded them to the GeneMANIA database, and obtained 10 genes which were most closely related to Hub genes, such as MX1, IFI44L, ISG15 and RSAD2. Then, the Hub genes were annotated by GO and analyzed by KEGG pathway. The results of enrichment analysis showed that the protein processing of endoplasmic reticulum, signal pathway related to virus infection, lipid and atherosclerosis, amino acid biosynthesis and cytoplasmic DNA sensing pathway were very important for the pathogenesis of pSS-IPF. TRRUST analysis showed that IRF1, SP1 and E2F1 were the three main transcription factors, and CASP7, TNFSF10, HSPA5 and PHGDH were also regulated by transcription factors. COREMINE was used to predict the key genes and pathways. The results showed that Renshen (Ginseng Radix et Rhizoma), Tusizi (Cuscutae Semen), Leigongteng (Radix et Rhizoma Tripterygii), Kushen (Sophorae Flavescentis Radix), Gouqi (Lycii Fructus), Gancao (Glycyrrhizae Radix et Rhizoma), Dongchongxiacao (Ophiocordyceps) and Renshenye (Ginseng Folium) were the core Chinese medicines for pSS-IPF.

In this study, the core genes and gene-enriched pathways of pSS-IPF were identified, the biological processes involved in pSS-IPF were discussed, and the Hub gene was verified by the verification data set, which provided the support for the selection of new targets for pSS-IPF treatment, predicted the therapeutic Chinese medicine for Hub gene, and provided a basis for the treatment and research of pSS-IPF.