A novel prognostic model based on epithelial cell progression genes identifies OAS1 as a suppressor of bladder cancer
Xu Su1, Hui Yu2, Miaoyu Zhang2
1Medical Research Center, The Third People's Hospital of Chengdu (Affiliated Hospital of Southwest Jiaotong University), College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Background:
Bladder cancer (BLCA) is a highly heterogeneous malignancy with an unpredictable prognosis. Tumour progression is closely linked to the complex tumour microenvironment (TME), particularly the role of epithelial cells. This study aims to identify key epithelial cell-derived signature genes driving tumour progression, construct a reliable prognostic model, and further explore the biological functions of a pivotal gene, OAS1, in BLCA.
Methods:
Single-cell RNA sequencing (scRNA-seq) data from public cohorts were analyzed to identify epithelial cell subpopulations and delineate their malignant progression trajectory. Genes significantly associated with this progression were identified through pseudotime analysis. Bulk RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) BLCA cohort were utilized for least absolute shrinkage and selection operator (LASSO) Cox regression to build a prognostic risk model. The model's predictive efficacy was validated in an independent Gene Expression Omnibus (GEO) cohort. Furthermore, in vitro experiments including CCK-8, transwell, and wound healing assays were conducted to investigate the impact of OAS1 on the proliferation, migration, and invasion capabilities of BLCA cells.
Results:
scRNA-seq analysis revealed a distinct epithelial cell subpopulation with high tumor-suppressive activity. A four-gene signature associated with tumor progression was successfully constructed into a prognostic model. Patients in the high-risk group exhibited significantly poorer overall survival in both the TCGA and validation cohorts. Multivariate Cox analysis confirmed the model as an independent prognostic factor. The risk score was significantly correlated with immune infiltration patterns and response to immunotherapy. Among the signature genes, OAS1 was identified as a critical factor. In vitro functional experiments demonstrated that knockdown of OAS1 markedly promoted the proliferation, migration, and invasion of BLCA cells.
Conclusion:
We established a novel prognostic model for BLCA based on epithelial cell tumor progression-associated genes, which serves as a robust predictor for patient outcomes and immunotherapeutic responsiveness. Our findings further highlight OAS1 as a key gene that suppresses the aggressive phenotypes of BLCA cells, suggesting it is a potential therapeutic target. This study provides valuable insights for precise prognosis and treatment stratification of BLCA patients.
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