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Liver hepatocellular carcinoma (LIHC) is a prevalent and highly aggressive form of liver cancer, characterized by increasing rates of incidence and mortality globally. Although numerous treatment options currently exist, they frequently result in insufficient clinical outcomes for those diagnosed with LIHC. This highlights the urgent need to identify new biomarkers that can enhance prognostic evaluations and support the development of more effective therapeutic strategies for LIHC. Through the use of the SwissTargetPrediction tool, we precisely identified molecular targets related to Sorafenib. Furthermore, analysis of RNA sequencing data from the TCGA-LIHC cohort uncovered 24 genes associated with different patient prognoses following Sorafenib therapy. Employing a clustering-based analytical approach, we assessed the connections between gene expression profiles, clinical outcomes, immune cell infiltration levels, and tumor stage progression. A prognostic framework was constructed by applying various machine learning techniques and subsequently validated across several independent datasets. Utilizing the XgBoost algorithm, MAPK12 emerged as a key regulatory gene influencing the prognosis of individuals with LIHC. The results of in vitro experiments demonstrated that knockdown of MAPK12 reduced the proliferation, metastasis, and tumor stemness-related sphere-forming ability of LIHC cells. These results underscore the promise of MAPK12 as a potential prognostic biomarker for LIHC and offer valuable insights for crafting personalized treatment approaches.
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http://dx.doi.org/10.1155/sci/9071464 | DOI Listing |
Nat Metab
September 2025
Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology (BRICS), Technische Universität Braunschweig, Braunschweig, Germany.
Itaconate is an immunomodulatory metabolite that alters mitochondrial metabolism and immune cell function. This organic acid is endogenously synthesized by tricarboxylic acid (TCA) metabolism downstream of TLR signalling. Itaconate-based treatment strategies are under investigation to mitigate numerous inflammatory conditions.
View Article and Find Full Text PDFCell Death Differ
September 2025
Graduate Institute of Physiology, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan, Republic of China.
Peroxisome proliferator-activated receptor alpha (PPARα) is a crucial transcriptional factor that regulates fatty acid β-oxidation and ketogenesis in response to fasting. However, the mechanisms underlying PPARα function remain unclear. This study identified a novel PPARα-binding protein-RING finger protein 128 (RNF128)-that facilitates PPARα polyubiquitination, resulting in the degradation and suppression of PPARα function during fasting.
View Article and Find Full Text PDFSurg Endosc
September 2025
Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands.
Background: The implementation of minimally invasive liver surgery (MILS) for perihilar (PHC) and intrahepatic cholangiocarcinoma (IHC) remains limited and a systematic review including only comparative studies of MILS versus the open approach is lacking. This systematic review and meta-analysis aimed to assess the safety and efficacy of minimally invasive surgery in patients with hilar and intrahepatic cholangiocarcinomas.
Methods: Systematic review in the PubMed, Embase, and Cochrane databases for original studies comparing at least five patients undergoing MILS with open liver surgery for PHC and IHC.
Nature
September 2025
Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Key Laboratory of RNA Innovation Science and Engineering, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Antigen-induced clustering of cell surface receptors, including T cell receptors and Fc receptors, represents a widespread mechanism in cell signalling activation. However, most naturally occurring antigens, such as tumour-associated antigens, stimulate limited receptor clustering and on-target responses owing to insufficient density. Here we repurpose proximity labelling, a method used to biotinylate and identify spatially proximal proteins, to amplify designed probes as synthetic antigen clusters on the cell surface.
View Article and Find Full Text PDFNat Commun
September 2025
Department of Biochemistry, University of Illinois, Urbana-Champaign, IL, USA.
Individuals with progressive liver failure risk dying without liver transplantation. However, our understanding of why regenerative responses are disrupted in failing livers is limited. Here, we perform multiomic profiling of healthy and diseased human livers using bulk and single-nucleus RNA- and ATAC-seq.
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