Deep Visual Proteomics to Understand a Rare Cancer - AusOmics 2025 скачать в хорошем качестве

Deep Visual Proteomics to Understand a Rare Cancer - AusOmics 2025

I gave this talk at the Aus-Omics conference in Cairns in May 2025. Something very different for me. I hope you find it interesting and useful. Deep Visual Proteomics reveals DNA replication stress as a hallmark of Signet Ring Cell Carcinoma. Sonja Kabatnik, Xiang Zheng, Georgios Pappas, Sophia Steigerwald, Stuart Adams, Matthew P Padula, Matthias Mann NNF Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark. Department of Biomedicine, Aarhus University, Denmark, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. Department of Anatomical Pathology, NSW Health Pathology, Nepean Hospital, NBMLHD, NSW, Australia. School of Life Sciences and Proteomics Core Facility, Faculty of Science, University of Technology Sydney, Ultimo, Australia. Abstract Signet Ring (SR) cell carcinoma (SRCC) is an increasingly prevalent subtype of gastric cancer, notorious for its late presentation and limited treatment success. Despite advancements in gastric cancer treatment, SRCC remains particularly challenging due to its late-stage diagnosis and the limited efficacy of conventional therapies, which have modest impact on survival and can diminish quality of life. In this study, we utilized Deep Visual Proteomics (DVP) to provide an in-depth spatial proteome analysis of SRCC presenting in different organs from a single patient, who is the presenting author. We identify extensive changes in DNA damage response (DDR) proteins, particularly in the pathways associated with ataxia-telangiectasia mutant (ATR) and DNA mismatch repair (MMR), suggesting replication stress as the leading factor of SRCC mutagenicity. In addition, we detected a significant enrichment in immune-related proteins, corroborated by high levels of cytotoxic T lymphocyte infiltration and expression of programmed cell death protein 1 (PD-1). Our study offers new insights into the biology of SRCC by identifying tumor-specific molecular features at the protein level, pointing to previously unconsidered therapeutic options. We elucidate the greater effectiveness of pembrolizumab immunotherapy in comparison to chemotherapy, underscoring the significance of tailored therapeutic strategies in the management of SRCC. Discussion of disease progression since the completion and publication of this study will also be discussed.