{
  "abstract": "Background Pancreatic cancer is a highly lethal malignancy with an immunosuppressive tumor microenvironment (TME) that promotes immune escape. Zinc finger protein 555 (ZNF555) is an incompletely characterized regulator, with the roles in pancreatic cancer progression and immune modulation remaining undefined. This study aimed to investigate the biological function and clinical significance of ZNF555 in pancreatic cancer.Methods Clinical data of 178 pancreatic cancer patients from The Cancer Genome Atlas (TCGA) were analyzed to explore the association between ZNF555 expression and overall survival using Pearson correlation, Regression, and Kaplan–Meier analyses. ZNF555 expression was evaluated in normal pancreatic epithelial cells (HPDE6-C7) and pancreatic cancer cell lines by RT-qPCR and Western blotting. ZNF555 knockdown in PANC-1 cells was established via lentiviral shRNA transduction. Cell biological functions were assessed using CCK-8, Scratch, and Transwell assays. An orthotopic xenograft mouse model was used to evaluate tumor growth in vivo, and tumor-infiltrating immune cells were characterized by flow cytometry. Statistical significance was defined as p<0.05.Results ZNF555 expression was correlated positively with overall survival in the pancreatic cancer patients ( R=0.235, p=0.0017), informing a trend towards survival improved in the high expression population (HR=0.66). Figure 1 illustrates the TCGA analysis, comprising ZNF555 expression distribution (IDDF2026-ABS-0518 Figure 1(A)), linear association with survival length (IDDF2026-ABS-0518 Figure 1(B)), and survival comparison between expression populations (IDDF2026-ABS-0518 Figure 1(C)). Compared to normal pancreatic epithelial cells, ZNF555 in pancreatic cancer cell lines was evidently downregulated at both the mRNA and protein levels (p<0.05). Figure 2 shows low expression across cancer cell lines (IDDF2026-ABS-0518 Figure 2(A-C)), relevant establishment of ZNF555 knockdown in PANC-1 cells (IDDF2026-ABS-0518 Figure 2(D–F)), and enhanced proliferative capacity following knockdown (IDDF2026-ABS-0518 Figure 2(G)). ZNF555 suppression visibly facilitated migration (56.7% vs 32.7%) and invasion (271 vs 112 cells). Figure 3 (IDDF2026-ABS-0518 Figure 3) indicates increased motility and invasiveness. ZNF555 knockdown promoted tumor growth in vivo (488 vs 267 mm3). Diminished CD45+ immune cell infiltration, increased immunosuppressive classifications (CD4+ T cells, M2 macrophages, M-MDSCs), and decreased CD8+ T and NK cells demonstrated vitalized immune escape.Conclusions ZNF555 is identified as a novel regulator of progression and immune escape in pancreatic cancer. Critical depletion drives aggressive tumor behavior and immunosuppressive TME remodeling, highlighting its potential as a therapeutic target for improving clinical outcomes.Abstract IDDF2026-ABS-0518 Figure 1Abstract IDDF2026-ABS-0518 Figure 2Abstract IDDF2026-ABS-0518 Figure 3",
  "authors": [
    {
      "affiliations": [
        "Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong"
      ],
      "name": "Instein Yaoying Xie"
    },
    {
      "affiliations": [
        "Department of Gastroenterology & Hematology, Wuzhou Red Cross Hospital, China"
      ],
      "name": "Bingbing Yu"
    }
  ],
  "title": "IDDF2026-ABS-0518 ZNF555 suppresses tumor progression and immune escape in pancreatic cancer",
  "uid": "5a020a4d-dda7-5281-bb28-329a85441b32"
}