The intricate crosstalk of various cell death forms was recently implicated in cancers, laying a foundation for exploring the association between cell death and cancers. Recent evidence has demonstrated that biological networks outperform snapshot gene expression profiles at discovering promising biomarkers or heterogenous molecular subtypes across different cancer types. In order to investigate the behavioral patterns of cell death-related interaction perturbation in colorectal cancer (CRC), this study constructed the interaction-perturbation network with 11 cell death pathways and delineated four cell death network (CDN) derived heterogeneous subtypes (CDN1-4) with distinct molecular characteristics and clinical outcomes. Specifically, we identified a subtype (CDN4) endowed with high autophagy activity and the worst prognosis. Furthermore, AOC3 was identified as a potential autophagy-related biomarker, which demonstrated exceptional predictive performance for CDN4 and significant prognostic value. Overall, this study sheds light on the complex interplay of various cell death forms and reveals an autophagy-related gene AOC3 as a critical prognostic marker in CRC.
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http://dx.doi.org/10.1038/s42003-024-05980-6 | DOI Listing |
Hepatology
January 2025
Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China.
Background And Aims: Immune checkpoint inhibitors (ICIs) have revolutionized systemic hepatocellular carcinoma (HCC) treatment. Nevertheless, numerous patients are refractory to ICIs therapy. It is currently unknown whether diet therapies such as short-term starvation (STS) combined with ICIs can be used to treat HCC.
View Article and Find Full Text PDFJ Appl Oral Sci
January 2025
Ningde Hospital Affiliated to Ningde Normal University, Department of Stomatology, Fujian, China.
Objective: This study aimed to investigate the role of transmembrane emp24 domain-containing protein 2 (TMED2) in oral squamous cell carcinoma (OSCC).
Methodology: A bioinformatics analysis was first conducted to explore TMED2 expression in OSCC and its relation with overall survival. The analysis results were further verified by assessing TMED2 expression levels in human normal oral keratinocyte cells and human OSCC cell lines using quantitative real-time polymerase chain reaction and the Western blot.
Sci Transl Med
January 2025
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO, USA.
Programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) interactions are targets for immunotherapies aimed to reinvigorate T cell function. Recently, it was documented that PD-L1 regulates dendritic cell (DC) migration through intracellular signaling events. In this study, we find that both preclinical murine and clinically available human PD-L1 antibodies limit DC migration.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses lead to severe respiratory illnesses and death in humans, exacerbated in individuals with underlying health conditions, remaining substantial global public health concerns. Here, we developed a bivalent replication-incompetent single-cycle pseudotyped vesicular stomatitis virus vaccine that incorporates both a prefusion-stabilized SARS-CoV-2 spike protein lacking a furin cleavage site and a full-length influenza A virus neuraminidase protein. Vaccination of K18-hACE2 or C57BL/6J mouse models generated durable levels of neutralizing antibodies, T cell responses, and protection from morbidity and mortality upon challenge with either virus.
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