PSMB9 Orchestrates Tumor Immune Landscape and Serves as a Potent Biomarker for Prognosis and T Cell-Based Immunotherapy Response
Abstract
1. Introduction
2. Materials and Methods
2.1. Expression Profiles
2.2. Prognosis Analysis
2.3. Genomic Alterations and Modification Analysis
2.4. Analysis of Tumor Stemness Correlations
2.5. Gene Set Enrichment Analyses
2.6. Immune Cell Infiltration Analysis
2.7. Immunotherapy Analysis
2.8. CAR-T Cell Generation
2.9. CRISPR/Cas9 Screening
2.10. Establishment of PSMB9KO Cell Line
2.11. Western Blot
2.12. Statistical Analysis
3. Results
3.1. PSMB9 Displays Dysregulated Expression Patterns Across Diverse Human Cancers
3.2. PSMB9 Expression Levels Exert Distinct Prognostic Impacts Across Different Tumor Types
3.3. PSMB9 Alteration Profiles and Their Role in Tumor Stemness
3.4. PSMB9 Associates with Tumor Immune Responses
3.5. Higher PSMB9 Reveals Superior Tumor Immune Cell Infiltration
3.6. PSMB9 Modulates Responses to ICIs
3.7. PSMB9 Plays a Potential Role in CAR-T Cell Therapy
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PSMB9 | Proteasome subunit beta type-9 |
MHC | Major histocompatibility complex |
CAR T | Chimeric antigen receptor T |
NSCLC | Non-small-cell lung cancer |
GTEx | Genotype-tissue expression |
IHC | Immunohistochemical |
HPA | Human Protein Atlas |
TCGA | The Cancer Genome Atlas |
GBM | Glioblastoma multiforme |
GBMLGG | Glioma (including GBM and LGG) |
LGG | Brain lower-grade glioma |
BRCA | Breast invasive carcinoma |
CESC | Endocervical adenocarcinoma |
LUAD | Lung adenocarcinoma |
ESCA | Esophageal carcinoma |
STES | Stomach and esophageal carcinoma |
KIRP | Kidney renal papillary cell carcinoma |
COAD | Colon adenocarcinoma |
PRAD | Prostate adenocarcinoma |
STAD | Stomach adenocarcinoma |
HNSC | Head and neck squamous cell carcinoma |
KIRC | Kidney renal clear cell carcinoma |
LIHC | Liver hepatocellular carcinoma |
SKCM | Skin cutaneous melanoma |
BLCA | Bladder urothelial carcinoma |
THCA | Thyroid carcinoma |
READ | Rectum adenocarcinoma |
OV | Ovarian serous cystadenocarcinoma |
PAAD | Pancreatic adenocarcinoma |
TGCT | Testicular germ cell tumors |
LAML | Acute myeloid leukemia |
KICH | Kidney chromophobe |
CHOL | Cholangiocarcinoma |
UCS | Uterine carcinosarcoma |
ALL | Acute lymphoblastic leukemia |
WT | Wilms tumor |
OS | Overall survival |
UVM | Uveal melanoma |
KIPAN | Pan-kidney cancer cohort (including KIRC, KIRP, KICH) |
SKCM-M | Skin cutaneous melanoma-metastatic |
SARC | Sarcoma |
DSS | Disease-specific survival |
DFI | Disease-free interval |
PFI | Progression-free interval |
THYM | Thymoma |
SKCM-P | Skin cutaneous melanoma-primary |
DNAss | DNA stemness score |
EREG-METHss | Epigenetic regulation of stemness-methylation score |
ENHss | Enhancer stemness score |
DEGs | Differential expression genes |
GSEA | Gene set enrichment analysis |
NFKB | Nuclear factor kappa-B |
TMB | Tumor mutational burden |
MSI | Microsatellite instability |
ICIs | Immune checkpoint inhibitors |
TIGER | Tumor Immunotherapy Gene Expression Resource |
ACT | Adoptive cell transfer |
SNV | Simple nucleotide variation |
CRISPR | Clustered regularly interspaced short palindromic repeat |
sgRNA | Single-guide RNA |
KO | Knockout |
PBMCs | Peripheral blood mononuclear cells |
ECL | Enhanced chemiluminescence |
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Signature Name | Description | AUC (Melanoma) | AUC (STAD) |
---|---|---|---|
PSMB9 | PSMB9 | 0.8164 | 0.7143 |
T cell-inflamed GEP | CCL5, CD27, CD274, CD276, CD8A, CMKLR1, CXCL9, CXCR6, HLA-DQA1, HLA-DRB1, HLA-E, IDO1, LAG3, NKG7, PDCD1LG2, PSMB10, STAT1 | 0.8229 | 0.7043 |
CAF | Cancer-associated fibroblasts | 0.5829 | 0.5731 |
TAM M2 | Tumor-associated macrophages | 0.8229 | 0.6174 |
IFNG | CXCL10, CXCL9, HLA-DRA, IDO1, IFNG, STAT1 | 0.818 | 0.6901 |
CD8 | CD8A, CD8B | 0.8438 | 0.7519 |
CD274 | CD274 | 0.8647 | 0.6817 |
TLS | CCL19, CCL21, CXCL13, CCR7, SELL, LAMP3, CXCR4, CD86, BCL6 | 0.7327 | 0.6383 |
TLS-melanoma | CD79B, CD1D, CCR6, LAT, SKAP1, CETP, EIF1AY, RBP5, PTGDS | 0.7279 | 0.4662 |
T cell dysfunction | Genes regulating dysfunction of T cells in TME | 0.6844 | 0.5656 |
T cell exclusion | Genes regulating T cell exclusion in TME | 0.7746 | 0.5622 |
MDSC | Myeloid-derived suppressor cells | 0.6924 | 0.4353 |
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Ma, X.; Zhu, Q.; Wu, Z.; Han, W. PSMB9 Orchestrates Tumor Immune Landscape and Serves as a Potent Biomarker for Prognosis and T Cell-Based Immunotherapy Response. Curr. Issues Mol. Biol. 2025, 47, 712. https://doi.org/10.3390/cimb47090712
Ma X, Zhu Q, Wu Z, Han W. PSMB9 Orchestrates Tumor Immune Landscape and Serves as a Potent Biomarker for Prognosis and T Cell-Based Immunotherapy Response. Current Issues in Molecular Biology. 2025; 47(9):712. https://doi.org/10.3390/cimb47090712
Chicago/Turabian StyleMa, Xinran, Qi Zhu, Zhiqiang Wu, and Weidong Han. 2025. "PSMB9 Orchestrates Tumor Immune Landscape and Serves as a Potent Biomarker for Prognosis and T Cell-Based Immunotherapy Response" Current Issues in Molecular Biology 47, no. 9: 712. https://doi.org/10.3390/cimb47090712
APA StyleMa, X., Zhu, Q., Wu, Z., & Han, W. (2025). PSMB9 Orchestrates Tumor Immune Landscape and Serves as a Potent Biomarker for Prognosis and T Cell-Based Immunotherapy Response. Current Issues in Molecular Biology, 47(9), 712. https://doi.org/10.3390/cimb47090712