Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma

Abstract

Abstract Background Gliomas account for the majority of fatal primary brain tumors, and there is much room for research in the underlying pathogenesis, the multistep progression of glioma, and how to improve survival. In our study, we aimed to identify potential biomarkers or therapeutic targets of glioma and study the mechanism underlying the tumor progression. Methods We downloaded the microarray datasets (GSE43378 and GSE7696) from the Gene Expression Omnibus (GEO) database. Then, we used weighted gene co-expression network analysis (WGCNA) to screen potential biomarkers or therapeutic targets related to the tumor progression. ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumors using Expression data) algorithm and TIMER (Tumor Immune Estimation Resource) database were used to analyze the correlation between the selected genes and the tumor microenvironment. Real-time reverse transcription polymerase chain reaction was used to measure the selected gene. Transwell and wound healing assays were used to measure the cell migration and invasion capacity. Western blotting was used to test the expression of epithelial-mesenchymal transition (EMT) related markers. Results We identified specific module genes that were positively correlated with the WHO grade but negatively correlated with OS of glioma. Importantly, we identified that 6 collagen genes (COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2) could regulate the immunosuppressive microenvironment of glioma. Moreover, we found that these collagen genes were significantly involved in the EMT process of glioma. Finally, taking COL3A1 as a further research object, the results showed that knockdown of COL3A1 significantly inhibited the migration, invasion, and EMT process of SHG44 and A172 cells. Conclusions In summary, our study demonstrated that collagen genes play an important role in regulating the immunosuppressive microenvironment and EMT process of glioma and could serve as potential therapeutic targets for glioma management.