Distinct cuproptosis patterns in hepatocellular carcinoma patients correlate with unique immune microenvironment characteristics and cell-cell communication, contributing to varied overall survival outcomes.

Background: Hepatocellular carcinoma (HCC), a prevalent cancer, is linked to cuproptosis in tumor progression. However, cuproptosis's impact on HCC prognosis and its role in the tumor microenvironment remain unclear. We aimed to explore the correlation between cellular cuproptosis and the immune microenvironment in HCC, providing potential immunotherapeutic insights. Methods: Examining cuproptosis-related genes and the immune microenvironment through consensus clustering and WGCNA. Risk models were constructed using LASSO Cox analysis and validated in an independent cohort. Gene expression data from The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database were utilized. We scored cuproptosis expression and explored immunoinfiltration and cell-cell communication. Differential signals in T_memory cells were compared across different cuproptosis levels. Results: Cuproptosis genes associated with fibroblast recruitment (GLS) and macrophage infiltration (FDX1). Liver cancer patients categorized into two subtypes based on cuproptosis gene expression. High expression of DLAT, GLS, and CDKN2A linked to immunosuppression (TGF-ß), while high FDX1, MTF1, LIAS, and LIPT1 expression enhanced communication with non-immune cells. Developed reliable prognostic signature score and nomogram using cuproptosis-related genes. Single-cell analysis revealed differences in T_memory and TAM infiltration based on cuproptosis scores, with SPP1 and MIF as dominant signaling molecules. Finally, the results of in vitro experiments showed that when DLAT or CDKN2A was knocked down, the proliferation, migration, and invasion of HCC cells were significantly decreased. Conclusion: Our study demonstrates that cuproptosis affects the immune microenvironment and cell-cell communication. Identified 9 genetic markers predicting survival outcomes and immunotherapy responses. Evaluating cuproptosis signaling can optimize immunotherapeutic strategies for hepatocellular carcinoma.

Triterpenoids of Ganoderma lucidum inhibited S180 sarcoma and H22 hepatoma in mice by regulating gut microbiota.

In order to explore effect of natural plant extracts on anti-tumor and prevent tumor development. The study assessed the antitumor effect of triterpenoids of Ganoderma lucidum (TGL) on S180 and H22 tumor bearing mice. A triterpene compound, 2α, 3α, 23-trihydroxy-urs-12-en-28-oic acid, was successfully isolated and purified from G. lucidum. S180 and H22 cells were subcutaneously inoculated in the left axilla of mice to establish a transplantable tumor model. After, the mice were orally treated with TGL and evaluated by tumor inhibition rate, organ index, and the serum index. The Bax and Bcl-2 proteins and gut microbiota was analyzed using western blot and 16S rDNA sequencing respectively. The results showed the tumor inhibition rates of TGL were higher than 40% in H22 and S180 tumor bearing mice. TGL had a protective effect on the spleen and thymus, and improved lipid peroxidation caused by the increased free radicals. TGL downregulated Bcl-2 and upregulated Bax. In particular, TGL treatment improved the reduction of gut microbiota richness and structure.