MTA1 promotes hepatocellular carcinoma progression by remodeling the immune microenvironment and regulating drug resistance gene networks: an integrated multi-database analysis.
- 1Department of Medicine, Tongling Polytechnic College, Tongling, China.
- 2Department of Hyperbaric Oxygen, The Second People's Hospital of Hefei, Hefei, China.
- 3Department of Nursing, Tongling Polytechnic College, Tongling, China.
Abstract
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. 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. 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. 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.
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BibTeX
@article{jin2026mta1,
title = {{MTA1 promotes hepatocellular carcinoma progression by remodeling the immune microenvironment and regulating drug resistance gene networks: an integrated multi-database analysis.}},
author = {Wen Jin and Liang Chen and Mei Yang and Jiankun Zhou and Bo Wang},
journal = {Journal of gastrointestinal oncology},
year = {2026},
month = oct,
doi = {10.21037/jgo-2026-1019},
url = {https://europepmc.org/article/MED/42996599},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - MTA1 promotes hepatocellular carcinoma progression by remodeling the immune microenvironment and regulating drug resistance gene networks: an integrated multi-database analysis.
AU - Wen Jin
AU - Liang Chen
AU - Mei Yang
AU - Jiankun Zhou
AU - Bo Wang
PY - 2026
DA - 2026/10/23
JO - Journal of gastrointestinal oncology
DO - 10.21037/jgo-2026-1019
UR - https://europepmc.org/article/MED/42996599
AB - 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. 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. 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. 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.
SN - 2078-6891
SN - 2219-679X
ER -