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Elevated Stanniocalcin-1 Expression in Uveal Melanoma Predicts Poor Patient Prognosis
Shin-Nosuke Yamashita1, Yoshiatsu Tanaka1, Shajedul Islam1,2
1Advanced Research Promotion Centre, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
Background/Aim:
Uveal melanoma (UVM) is the most prevalent primary intraocular malignancy, accounting for 3-5% of all melanomas. Despite its rarity, particularly in Japan (~2 cases per 100,000 individuals annually), UVM exhibits highly aggressive behavior, with nearly 50% of patients developing distant metastases. Once metastasized, the prognosis remains dismal, with a median survival of only 4-5 months. Identifying prognostic biomarkers and potential therapeutic targets is imperative to improve clinical outcomes. Stanniocalcin-1 (STC-1) is a glycoprotein hormone implicated in calcium and phosphate homeostasis. Recent studies have linked STC-1 overexpression to tumor progression, poor prognosis, and increased metastatic potential in various malignancies. However, the prognostic significance and mechanistic role of STC-1 in UVM remain unexplored.
Materials And Methods:
To elucidate the clinical relevance of STC-1 in UVM, we analyzed publicly available transcriptomic datasets using GEPIA2 and UALCAN, assessing STC-1 mRNA expression across disease stages and its correlation with patient survival. In parallel, single-cell RNA sequencing (scRNA-seq) datasets were utilized to identify the cellular sources of STC-1 within the UVM tumor microenvironment and to investigate its association with specific functional cellular states.
Results:
STC-1 expression was significantly up-regulated in stage IV UVM tumors compared to stage III (n=4 and 36, respectively). Moreover, elevated STC-1 expression was inversely correlated with overall survival, suggesting its potential role in disease progression. scRNA-seq analysis revealed that STC-1 is expressed by both tumor cells and fibroblasts, indicating a possible cooperative mechanism that may drive tumor progression.
Conclusion:
These findings suggest that STC-1 serves as a potential prognostic biomarker in UVM, providing novel insights into its role in tumor biology. Further investigation is warranted to explore its therapeutic implications and mechanistic contributions to UVM progression.
Insights
Stanniocalcin-1 (STC-1) is upregulated in advanced uveal melanoma (UVM) and linked to poorer survival. STC-1, expressed by tumor cells and fibroblasts, may serve as a prognostic biomarker for UVM.
Area of Science:
- Oncology
- Molecular Biology
- Ophthalmology
Background:
- Uveal melanoma (UVM) is an aggressive intraocular cancer with poor prognosis post-metastasis.
- Identifying prognostic biomarkers is crucial for improving UVM patient outcomes.
- Stanniocalcin-1 (STC-1) is implicated in various cancers, but its role in UVM is unknown.
Purpose of the Study:
- To investigate the prognostic significance of STC-1 in UVM.
- To explore the cellular sources and potential mechanisms of STC-1 in the UVM tumor microenvironment.
Main Methods:
- Analysis of publicly available transcriptomic datasets (GEPIA2, UALCAN) for STC-1 mRNA expression and survival correlation.
- Single-cell RNA sequencing (scRNA-seq) to identify STC-1 expressing cells and their functional states within UVM.
Main Results:
- STC-1 mRNA expression was significantly higher in stage IV UVM compared to stage III.
- Elevated STC-1 expression inversely correlated with overall patient survival.
- scRNA-seq identified both UVM cells and fibroblasts as sources of STC-1, suggesting a cooperative role.
Conclusions:
- STC-1 is a potential prognostic biomarker for uveal melanoma.
- STC-1 may play a role in UVM progression through interactions between tumor cells and fibroblasts.
- Further research is needed to explore STC-1's therapeutic potential in UVM.
