MTA1 promotes hepatocellular carcinoma progression by remodeling the immune microenvironment and regulating drug resistance gene networks: an integrated multi-database analysis
Year: 2026
Type: article
Abstract: Background: Resistance to immunotherapy, chemotherapy, and targeted therapy remains a significant challenge in hepatocellular carcinoma (HCC). The relationships between metastasis-associated protein 1 (MTA1), multidrug resistance (MDR) networks, and the tumor immune microenvironment remain poorly understood. This study investigated associations between MTA1 expression, prognosis, treatment-related genes, and immune-related features in HCC.Methods: Bioinformatics analyses integrated data from the Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA), and the Human Protein Atlas (HPA). Pearson correlation analysis was employed to characterize the co-expression patterns between MTA1 and genes associated with different forms of therapeutic resistance. Clinical tissue immunohistochemistry assessed MTA1 expression and cellular localization. Candidate MTA1-associated compounds were screened using the Comparative Toxicogenomics Database (CTD), and their predicted interactions with MTA1 were assessed by molecular docking. Gene set enrichment analysis (GSEA) examined MTA1-associated signaling pathways.Results: MTA1 was markedly upregulated in HCC tissues, and elevated expression was significantly associated with shorter overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). MTA1 expression correlated positively with infiltration scores for T helper cells, central memory T cells, and T helper 2 cells, and negatively with scores for dendritic cells, plasmacytoid dendritic cells, and γδ T cells. Positive correlations were also observed with the immune checkpoint genes CD274 and PDCD1. MTA1 expression was significantly and positively correlated with genes related to chemotherapy, lenvatinib, sorafenib, broader tyrosine kinase inhibitor (TKI) treatment, and immunotherapy. Immunohistochemistry showed predominantly nuclear localization of MTA1. Estradiol and ethinyl estradiol were identified as candidate compounds, with predicted docking scores of −8.1 and −8.8, respectively. GSEA associated MTA1 expression with enrichment of treatment-related signaling pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) and Wnt signaling.Conclusions: MTA1 expression was associated with prognosis, immune-related features, and treatment-related gene expression in HCC. These findings support further evaluation of MTA1 as a prognostic biomarker and candidate therapeutic target, and provide a basis for experimental investigation of MTA1-related mechanisms and candidate compounds.
Authors: Wen Jin, Liang Chen, Mei Yang, Jiankun Zhou, Bo Wang
Institution: Tongling Polytechnic
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224087842