DBF4B promotes hepatocellular carcinoma progression by regulating CCNA2 and PSMD11 expression

ULBP1 is a prognostic biomarker associated with immune suppression in breast cancer

ULBP1 may serve as a potential novel prognostic biomarker in BC, and targeting ULBP1 may provide a new therapeutic strategy for BC.

IFFO2 Promotes Tumor Progression and Serves as a Prognostic Biomarker in Liver Hepatocellular Carcinoma

Functional enrichment analysis revealed that IFFO2 is significantly associated with immune regulation, cell cycle, and complement activation pathways, and its strong association with adverse prognosis and its potential to modulate the immune microenvironment underscore its dual potential as a diagnostic biomarker and a promising therapeutic target.

Overexpression of TCF7L2 promotes the viability and migration of MHCC-97H human hepatocellular carcinoma cells by upregulating MT-ND4L

Background Hepatocellular carcinoma (HCC) is a highly aggressive cancer with high metabolic adaptability. TCF7L2, a transcription factor implicated in type 2 diabetes and cancer, is overexpressed in HCC. However, its specific role in HCC metabolic reprogramming is not well defined. We aimed to elucidate the previously unrecognized molecular mechanisms through which TCF7L2 impacts HCC progression. Methods To investigate the function of TCF7L2, a stable MHCC-97H cell line with TCF7L2 overexpression was established via lentiviral transduction. Cell viability and migration were assessed by Cell Counting Kit-8 (CCK-8) and Transwell assays. Transcriptomic profiling [RNA sequencing (RNA-seq)] was performed to identify differentially expressed genes (DEGs). Functional enrichment analysis [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA)] and bioinformatics promoter analysis (the JASPAR CORE database) were conducted. Clinical correlations, survival analysis, and tumor microenvironment (TME) interrogation were performed using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort and single-cell datasets [Human Protein Atlas (HPA), CellChat]. Drug sensitivity was predicted via the Genomics of Drug Sensitivity in Cancer (GDSC) database. Results TCF7L2 overexpression significantly promoted HCC cell proliferation and migration. Transcriptomic analysis revealed that TCF7L2 drives a profound metabolic shift, with key enrichments in lipid homeostasis, fatty acid β-oxidation, and the PI3K/Akt pathway. Mechanistically, TCF7L2 directly binds to the promoter of CPT1A, the rate-limiting enzyme of fatty acid oxidation, and indirectly upregulates the mitochondrial gene MT-ND4Lvia a strong positive correlation with the mitochondrial transcription factor TFAM. In clinical cohorts, TCF7L2 was overexpressed in HCC and its expression correlated positively with MT-ND4L, MKI67, and SNAI1, and served as a predictor of poor overall survival (OS). Furthermore, TCF7L2-high tumors were enriched in hepatic progenitor cell (HPC)-like niches, mediated by enhanced ANGPTL4 signaling. High TCF7L2 expression predicted increased sensitivity to PI3K/mTOR pathway inhibitors. Conclusions TCF7L2 acts as a master metabolic regulator in HCC, coordinating lipid catabolism and mitochondrial biogenesis to drive aggressive tumor behavior. It further remodels the TME towards an HPC-like state and predicts sensitivity to metabolic-targeted therapies. These findings identify TCF7L2 as a key prognostic biomarker and a promising therapeutic target.

SLC25A45 as a prognostic biomarker promotes malignant progression via mutant p53 in hepatocellular carcinoma

Background SLC25A45 belongs to the mitochondrial trimethyllysine carrier protein family. To date, its role in tumor development has not been fully elucidated. Previous studies have demonstrated its pro-tumor function in ovarian cancer; however, research on the expression characteristics, biological roles and underlying regulatory pathways of SLC25A45 in hepatocellular carcinoma (HCC) is limited. This study aims to explore the expression, functional roles, and regulatory pathways of SLC25A45 in HCC. Methods This study examined SLC25A45 expression and clinical relevance in HCC using publicly available transcriptomic data. SLC25A45 knockdown cell lines were constructed using PLC/PRF/5, Huh7, and Huh1 cells. Functional assays, including cell proliferation and colony formation assays, were then conducted. To investigate the effects of SLC25A45 knockdown on the malignant phenotypes of HCC cells in vitro, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analyses were performed to identify potential underlying mechanisms, which were subsequently validated by experimental assays. Results SLC25A45 was elevated in clinical HCC specimens, and high SLC25A45 expression was correlated with disease progression and poor overall survival (OS). In vitro functional assays demonstrated that SLC25A45 silencing reduced HCC cell proliferation and colony formation. Mechanistically, GSEA indicated that high SLC25A45 expression was significantly enriched in the p53 signaling pathways. SLC25A45 knockdown in HCC cells led to a significant increase in wild-type p53 protein expression, but a substantial decrease in mutant p53 expression. Conclusions SLC25A45 is a potential prognostic indicator and may drive HCC tumorigenesis and progression through the differential modulation of the p53 signaling pathways.

Identification of a metastasis-associated prognostic gene signature in osteosarcoma through integrated bioinformatics and functional analysis

MSTO1 promotes hepatocellular carcinoma progression and represents a potential target for immunotherapy.

The incidence of hepatocellular carcinoma (HCC) has increased over recent decades. While significant progress has been achieved in immunotherapy, the five-year survival rate is still unsatisfactory because of the low response rate and acquired resistance in a few patients, which reflects the complexity of the immune microenvironment in HCC. In this study, TCGA-LIHC, ICGC-LIRI-JP, and GEO data sets were used to verify the role of MSTO1 in the pathogenesis and progression of HCC. We then identified spatial distribution and cellular source of MSTO1 expression using single-cell RNA-sequencing and spatial transcriptomics. We investigated possible downstream mechanism of MSTO1 with virtual knockdown, DepMap, and scRNA-seq analysis. We evaluated the importance of MSTO1 for clinical treatment from the perspective of immune infiltration, cell-cell communication, immunotherapy databases, and orthotopic HCC model treated by AAV8-shMsto1. MSTO1 was upregulated in HCC and correlated with clinical features, including poor overall survival and advanced tumor stage. Functionally, MSTO1 promoted colony formation, migration, invasion, and in vivo progression of HCC. Mechanistically, HSP90AB1 was a potential downstream effector of MSTO1, related to MYC signaling pathway. Additional pathway analysis of the trajectories and metabolites revealed a correlation between the MSTO1+ malignant cells with MYC signaling, metabolic pathway, as well as an immunosuppressive microenvironment. MSTO1 knockdown and anti-PD-1 therapy might play a synergistic role in the treatment of HCC. Overall, MSTO1 plays an important role during the development of HCC, and it was also associated with survival or response to immunotherapy. The progression of HCC may be associated with HSP90AB1 and MYC, and targeting MSTO1 may effectively enhance the efficacy of anti-PD-1 therapy.