| Expression pattern: |
UP |
| Associated gene: |
CD8+ T cells, IFN-gamma, CXCL9, CXCL10, IL-2, TGF-beta, IL-1beta |
| Associated microRNA: |
- |
| Biological function: |
reduces sensitivity to ICIs by promoting proliferation, clonogenesis, invasion and migration, inhibiting apoptosis; promotes NSCLC progression; induces CD8+ T-cell exhaustion |
| Molecular mechanism: |
immune suppression via inducing CD8+ T-cell exhaustion and altering cytokine/chemokine milieu; secreted/packaged into extracellular vesicles |
| Biological pathway or process: |
proliferation (promotes); invasion (promotes); migration (promotes); apoptosis (inhibits); immune regulation (other); T cell exhaustion (promotes) |
| Detected method: |
Q
M
|
| Validation methods: |
RT-qPCR; Microarray; Clinical Sample Validation; Cohort Study; ROC Analysis; Survival Analysis; Transfection; CCK8; Colony Formation Assay; Transwell Assay; Wound Healing Assay; Annexin V/PI Flow Cytometry; Western Blot; ELISA; Flow Cytometry（Non-apoptosis/cycle）; IHC (Immunohistochemistry); TUNEL; In Vivo Animal Model |
| Clinical significance: |
Upregulated in NSCLC patients with ICIs resistance; high diagnostic efficiency for ICIs resistance (AUC = 0.98); higher expression associated with shorter PFS |
| Description: |
circ_PPAPDC1A is upregulated in NSCLC with acquired ICIs resistance and is enriched in circulating extracellular vesicles. Functionally, it decreases anti-PD-1 efficacy by promoting malignant phenotypes (proliferation, clonogenesis, invasion/migration) and inhibiting apoptosis, and in vivo it induces an immunosuppressive state with CD8+ T-cell exhaustion. Clinically, EV circ_PPAPDC1A shows strong diagnostic performance for ICIs resistance and high expression predicts shorter PFS. |
| Confidence score: |
0.7074 |