Abstract
Previous reports have suggested a link between pulmonary tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), and the development of lung adenocarcinoma (LUAD) and sarcoidosis. Furthermore, these lung diseases share certain clinical similarities that can challenge differential diagnosis in some cases. Here, through comparison of lung transcriptome-derived molecular signatures of TB, LUAD and sarcoidosis patients, we identify certain shared disease-related expression patterns. We also demonstrate that MKI67, an over-expressed gene shared by TB and LUAD, is a key mediator in Mtb-promoted tumor cell proliferation, migration, and invasion. Moreover, we reveal a distinct ossification-related TB lung signature, which may be associated with the activation of the BMP/SMAD/RUNX2 pathway in Mtb-infected macrophages that can restrain mycobacterial survival and promote osteogenic differentiation of mesenchymal stem cells. Taken together, these findings provide novel pathogenic links and potential molecular markers for better understanding and differential diagnosis of pulmonary TB, LUAD and sarcoidosis.
Highlights
Previous reports have suggested a link between pulmonary tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), and the development of lung adenocarcinoma (LUAD) and sarcoidosis
Hierarchical clustering followed by Reactome pathway enrichment analysis of these transcripts indicated that TB, LUAD, and sarcoidosis were largely correlated with overrepresented extracellular matrix (ECM) organization-associated pathways such as those involved in collagen degradation, assembly of collagen fibrils and other multimeric structures, as well as collagen biosynthesis and modifying enzymes (Fig. 1b)
Using Kaplan–Meier analysis, we identified a total of 65 TB-LUADshared Differentially expressed genes (DEGs) whose expression was significantly correlated with the overall survival (OS) of LUAD patients from The Cancer Genome Atlas (TCGA) (Fig. 1c and Supplementary Data 5)
Summary
Previous reports have suggested a link between pulmonary tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), and the development of lung adenocarcinoma (LUAD) and sarcoidosis. We reveal a distinct ossification-related TB lung signature, which may be associated with the activation of the BMP/SMAD/RUNX2 pathway in Mtb-infected macrophages that can restrain mycobacterial survival and promote osteogenic differentiation of mesenchymal stem cells. Taken together, these findings provide novel pathogenic links and potential molecular markers for better understanding and differential diagnosis of pulmonary TB, LUAD and sarcoidosis. We unravel distinct lung modular signatures and molecular markers of TB, LUAD, and sarcoidosis, and verify an ossification-related TB lung signature, which is probably associated with the activation of BMP/SMAD/RUNX2 pathway in Mtb-infected macrophages that controls mycobacterial survival and promotes osteogenic differentiation of mesenchymal stem cells (MSCs). Our findings provide new insights into Mtb pathogenesis and may contribute to differential diagnosis of TB, LUAD, and sarcoidosis
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