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3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
Exploring ZPLD1 as a Prognostic Indicator and Therapeutic Target in Bladder Cancer.
Yiwen Chen1, Hanliang Zhu1, Meiting Lao2
1Department of Urology, Longgang District Central Hospital of Shenzhen, Shenzhen, 518166, Guangdong Province, China.
Zona-Pellucida-like Domain-containing Protein 1 (ZPLD1) is a novel biomarker for bladder cancer (BLCA). High ZPLD1 indicates poor prognosis and influences immune response and drug sensitivity in BLCA patients.
Area of Science:
- Uro-oncology
- Molecular diagnostics
- Cancer biomarkers
Background:
- Bladder cancer (BLCA) has a rising incidence and poor prognosis, necessitating new prognostic markers and therapeutic targets.
- The extracellular-matrix gene Zona-Pellucida-like Domain-containing Protein 1 (ZPLD1) has not been previously studied in BLCA.
Purpose of the Study:
- To investigate the expression, prognostic value, immune contexture, and druggability of ZPLD1 in BLCA.
- To establish ZPLD1 as a potential biomarker for risk stratification and therapeutic targeting in BLCA.
Main Methods:
- Multi-level integrative analysis of TCGA-BLCA and GSE121711 datasets.
- RNA-seq, differential expression analysis, survival analysis (Kaplan-Meier, Cox regression), GSEA, ssGSEA, ESTIMATE, and qRT-PCR.
- Correlation analysis with cancer stemness, drug sensitivity, and genomic alterations.
Main Results:
- ZPLD1 was significantly upregulated in BLCA tissues and served as a diagnostic marker (AUC=0.704).
- High ZPLD1 independently predicted poorer overall and disease-specific survival.
- ZPLD1 correlated with immune cell infiltration (Th1, macrophages, neutrophils), immune checkpoints (PD-L1, CTLA-4, LAG-3, PD-1), reduced cancer stemness, and altered sensitivity to specific chemotherapies and targeted agents.
Conclusions:
- ZPLD1 is a novel, independent prognostic biomarker for poor outcomes in BLCA.
- ZPLD1 influences the tumor immune microenvironment and drug response, suggesting its role in risk stratification.
- ZPLD1 represents a potential therapeutic target for precision oncology strategies in BLCA, requiring further validation.
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