Abstract
BACKGROUND: TBX5 is a key protein regulated by the TGF-β/Smad3 pathway, which plays a significant role in colorectal cancer (CRC) development. This study aims to investigate the interplay between Gegen Qinlian Decoction (GQD), TBX5, and CRC mechanisms. METHODS: The Cancer Genome Atlas (TCGA-CRC) dataset from the TCGA database was utilized for the study. Differential expression analysis was conducted to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Subsequently, analyses were performed focusing on TBX5, encompassing pan-cancer evaluation, protein-level expression assessment, and enrichment analysis. Correlation analyses were carried out to investigate the relationships between TBX5, clinical characteristics, prognosis, and key pathways in CRC. Furthermore, immune analysis, network construction, drug prediction, and molecular docking studies were conducted. RESULTS: A total of 1,834 differentially expressed genes (DEGs) were identified in TCGA-CRC. TBX5 exhibited elevated expression levels in CRC compared to other cancer types and normal tissues, correlating with lower survival rates in the high TBX5 expression cohort. Additionally, SPTBN4, RP11-35N6.1, CHD5, SLC4A8, KLHL32, MAP2, and ATP8A2 were found to be prognostic markers for patient outcomes. Age, N, and M stages were identified as significant independent prognostic factors for CRC. Notably, there was a significant upregulation of cell stemness, epithelial-mesenchymal transition (EMT), and angiogenesis-related genes in the high TBX5 expression group. Furthermore, the prognostic significance of 10 immune cell types, including mast cells, myeloid-derived suppressor cells (MDSCs), and monocytes, was evident. Thirteen key miRNAs were identified, and an mRNA-miRNA-lncRNA regulatory network was constructed, revealing relationships such as TBX5-hsa-mir-1270-TMPO-AS1. Molecular docking analyses demonstrated favorable binding of active compounds like formononetin and cinnamic acid to TBX5. CONCLUSION: Our findings suggested a potential association between GQD, TBX5-related genes, and CRC progression, which could provide valuable insights for the diagnosis and treatment of CRC.