Human hepatocellular carcinoma samples proteomic analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Yungang Xu
PROVIDER: PXD053184 | iProX | Mon Jun 17 00:00:00 BST 2024
REPOSITORIES: iProX
Similar Datasets
Project description:Lysine metabolism reprogramming reshapes the immune microenvironment and induces immunotherapy tolerance in liver cancer
| PRJNA1137233 | ENA
Project description:Liver cancer is one of the most common malignant tumors worldwide, and its high aggressiveness and recurrence rate pose a major challenge. Metabolic reprogramming is one of the cancer hallmarks and allows tumor cells to adapt to drastic changes, supporting their rapid growth, survival, and proliferation under various conditions. The metabolic reprogramming of several amino acids within tumors profoundly affects the function of the immune cells. Furthermore, arginine and various other amino acids are now being widely studied as potential targets for anti-tumor therapy. However, the role of lysine metabolic reprogramming in tumors remains largely unexplored. This study aims to reveal the relationship between lysine metabolism reprogramming and the prognosis of liver cancer, the tumor immune microenvironment (TIME), and responses to immunotherapy through multi-omics analysis. Combined transcriptomic and proteomic analyses revealed a significant downregulation of lysine metabolism in tumor tissues against normal tissue adjacent to the tumor from liver cancer patients. Subsequently, we constructed a lysine metabolism score (LM score) based on nine lysine metabolic genes to stratify liver cancer patients into high and low lysine metabolism subtypes. The LM score exhibited potential in predicting both survival and immunotherapy response in liver cancer. Furthermore, significant differences were observed in prognosis, clinical staging, TIME, and immunotherapy outcomes between the subtypes with low and high lysine metabolism. In the subtype of low lysine metabolism, an immunosuppressive TIME predominated, correlating with poorer patient survival and anti-tumor immune responses. In conclusion, we uncover that disturbed lysine metabolism promotes the formation of the immunosuppressive TIME, thereby inducing immunotherapy resistance and advancing liver cancer progression. This provides an effective theoretical reference for elucidating the mechanism of immunotherapy resistance in liver cancer and seeking new therapeutic strategies.
2025-12-02 | GSE272510 | GEO
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world. Mitochondrial fission regulator 2 (MTFR2) is involved in the development of various cancers. However, the roles of MTFR2 in HCC remain unknown. In this study, we conducted a comprehensive analysis of MTFR2 in HCC, which was generated from integrative MTFR2 analyses of eight HCC cell lines, and three datasets (public dataset, real-world dataset, immunotherapy dataset) derived from bulk HCC tissues, survival and immunotherapy data. We demonstrated that the expression level of MTFR2 is up-regulated in HCC, leading to poor prognosis. MTFR2 is positively correlated with the level of immune cell infiltration, multiple immune checkpoints and immunotherapy response prediction pathways, and act important role in cancer-immunity cycle. In conclusion, our work indicates that MTFR2 can shape a barrier of immune microenvironment and result in poor prognosis in hepatocellular carcinoma, but the immune barrier may be broken by immunotherapy.
2022-09-01 | GSE212529 | GEO
Project description:Our research demonstrates that in hepatocellular carcinoma (HCC), tumor cells outcompete T cells for lysine (Lys) by overexpressing the SLC3A2 transporter, thereby reducing Lys availability within the tumor microenvironment. This lysine deprivation results in decreased STAT3 levels in T cells, inhibiting their proliferation and effector functions, which ultimately accelerates tumor progression. Additionally, we identified a c-Myc-SLC3A2 regulatory axis activated by Lenvatinib, enhancing the sensitivity of HCC to the combined treatment with Lenvatinib and Lys.
2024-12-23 | GSE284633 | GEO
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer death, with limited treatment options for advanced stages. Although PD-1 inhibitors like nivolumab and pembrolizumab are approved for advanced HCC, their effectiveness is often hampered by the immunosuppressive tumor microenvironment, driven by hypoxia-driven CXCL12/CXCR4 axis activation. Herein, we develop 807-NP, a lipid-coated tannic acid nanoparticle to encapsulate and deliver BPRCX807, a potent antagonist of CXCR4, into HCC tumors. 807-NP enhances pharmacokinetics and improves tumor availability of BPRCX807 without systemic toxicity. Our findings show that 807-NP blocks the CXCR4/CXCL12 pathway, inhibiting Akt and mTOR activation in HCC cells and M2 macrophages, promoting their repolarization to an anti-tumor M1 phenotype. In orthotopic murine HCC models, systemic administration of 807-NP significantly remodels the immunosuppressive tumor microenvironment by reprogramming tumor associated macrophages (TAMs) towards an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. This suppresses primary tumor growth and metastasis while enhancing the efficacy of cancer immunotherapies, including PD-1 blockades and whole cancer cell vaccines, by facilitating T cell activation. Our work demonstrates the potential of nanotechnology-enabled delivery of CXCR4 antagonists to improve cancer immunotherapy.
2025-08-07 | GSE276234 | GEO
Project description:Increasing evidence indicates that activation of oncogenic pathways contributes to an unfavourable tumour immune microenvironment (TIME), ultimately resulting in resistance to immunotherapy. Here, we aim to identify a critical oncogenic pathway involved in an antigen-expressing c-MYC-lucOSOE/Tp53KO HCC mouse model that simulates immune response against tumour-associated antigens in human HCC. To investigate the intrinsic oncogenic pathway enriched in tumours exhibiting immune evasion, tumour tissues were harvested from c-MYC-lucOE/Tp53KO mice and immune-escaped c-MYC-lucOSOE/Tp53KO mice for DIA proteomics.
2025-09-18 | PXD058362 | Pride
Project description:Spatial transcriptome on human hepatocellular carcinoma
| PRJEB62485 | ENA
Project description:Immunotherapy becomes standard-of-care treatment of hepatocellular carcinoma (HCC) but still limited number of patients benefit from immunotherapy due to the high heterogeneity of tumor immune-microenvironment (TIME) of HCC patients. Therefore, it is important to stratify patients who benefit from immunotherapy by analyzing the molecular and immunological diversity of HCC. Since non-viral HCC is rapidly increasing all over the world, in this study, we focused on non-viral HCC and aimed to identify immunotherapy-susceptible patients through multi-omics. Global RNA sequencing of surgically-resected tumor tissues in 113 non-viral HCC patients was performed. Unsupervised hierarchical clustering classified non-viral HCCs into 3 molecular classes associated with patient prognosis and corresponding driver gene abnormality. We further identified the immune-enriched but -exhausted subclass with intratumor steatosis in non-viral HCCs, characterized by T-cell exhaustion, infiltration of M2 macrophage and cancer-associated fibroblast (CAF), high PD-L1 expression, and TGF-β signaling activation..
2022-05-22 | GSE190967 | GEO
Project description:We report a tissue-derived KLRG1-ILC2s highly expressing CD69 in HCC, which are distinguished from circulating ones from portal vein and peripheral blood. Relief of KLRG1 inhibitory signaling, the HCC-induced ILC2s tend to shape an immunosuppressive tumor microenvironment through CXCL2/neutrophil axis. Furthermore, the abundance of ILC2s in HCC correlated with the recurrence and progression free survival (PFS) of HCC patients indicated ILC2s being an emerging target for HCC immunotherapy.
2021-11-24 | GSE151895 | GEO
Project description:AimsSeveral studies have shown the presence of helicobacter species in the human biliary tract and in the intestinal tract of animals. Experimental infection by Helicobacter hepaticus in mice causes chronic hepatitis and hepatocellular carcinoma (HCC). This study investigated whether helicobacter species could be detected in the liver of patients with HCC.MethodsLiver samples from 20 patients with primary liver carcinoma diagnosed by histopathology and 16 controls without primary liver carcinoma were studied. Histology with standard and immunohistochemical stains, culture, and polymerase chain reaction (PCR) amplification using helicobacter genus specific 16S rRNA primers were used to detect the presence of bacteria. Amplified products were identified by Southern hybridisation and sequencing. A search for other genes specific for Helicobacter pylori was also performed.ResultsHelicobacter species 16S rDNA was found in eight of 20 samples of primary liver carcinoma, whereas none of the controls harboured this rDNA. Six helicobacter specific PCR amplicons were sequenced and were found to have 98.5-99.0% similarity to the 16S rDNA of H pylori. Of the eight positive samples, seven were positive in PCR using 26 kDa protein primers and six showed morphological and immunohistochemical evidence of H pylori. The cagA and glmM genes were detected in only two samples. The vacA and rps4 genes were not detected.ConclusionsHelicobacter can be present in the liver of patients with primary liver carcinoma and is probably linked to the carcinogenic process in the liver.
| S-EPMC1770525 | biostudies-literature