Identification and clinical validation of endoplasmic reticulum genes related to pulmonary tuberculosis

Tuberculosis caused by Mycobacterium tuberculosis is a serious infectious disease. Previous studies have shown that endoplasmic reticulum (ER) stress plays an important role in various infectious diseases. This study aims to identify potential ER stress-related genes in tuberculosis by analyzing differentially expressed genes (DEGs) and to explore the role of ER stress in Mycobacterium tuberculosis infection. This study identified 10 endoplasmic reticulum stress-related differentially expressed genes (ERSRDEGs) by standardizing and analyzing the differential expression of the dataset GSE114911. GO and KEGG enrichment analysis found that ERSRDEGs are significantly involved in neutrophil migration 17/TNF signaling pathway. Protein-protein interaction network identified four hub genes ( IL-1B , CCL20, IL-1A , TNF), among which IL-1B showed highly significant differential expression in the independent dataset GSE147964, demonstrating excellent diagnostic performance (AUC = 0.93), and was validated by ELISA for its high expression in the serum of tuberculosis patients. Immune infiltration analysis showed that the infiltration of M1 macrophages increased in the tuberculosis infection group, and IL-1B was strongly positively correlated with M1 macrophages. In addition, the study also analyzed the correlation between IL-1A and IL-1B with clinical indicators (inflammatory factors, D-dimer). According to the analysis results, IL-1B was positively correlated with IL-6, TNF, and IFN-γ, while IL-1A was positively correlated with D-dimer.Our findings emphasize the critical role of ER stress-related genes in the pathophysiology of Mycobacterium tuberculosis infection.