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Published on: October 11, 2019
Lower SYNJ2BP Gene Expression Is Associated With Poor Survival Outcome and Treatment Response in Clear Cell Renal
Marilyn D Saulsbury1, Simone O Heyliger1, Emanuela Taioli2
1School of Pharmacy, Department of Pharmaceutical Sciences, Hampton University, Hampton, VA, U.S.A.
Background/Aim:
Clear cell renal cell carcinoma (ccRCC), the most prevalent form of kidney cancer, often presents or recurs as an advanced, aggressive, and lethal disease. Thus, biomarkers are needed to identify patients at risk of developing advanced-stage or treatment-resistant ccRCC. SYNJ2BP, a cytoplasmic scaffolding protein, regulates ACVR2 activity, a key mediator of signaling pathways involved in tumor progression and metastasis. This study aimed to ascertain if SYNJ2BP, a gene highly expressed in normal kidney tissue, may serve as a predictive biomarker for ccRCC.
Materials And Methods:
Bioinformatic analysis and immunohistochemistry were applied to investigate the relationship between SYNJ2BP expression, the immune landscape, and survival outcomes in ccRCC. We utilized data from publicly available databases, including The Cancer Genome Atlas, Gene Set Cancer Analysis (TCGA), and various other databases.
Results:
In-silico analyses revealed that SYNJ2BP expression was significantly down-regulated in ccRCC (Log2FC=0.40, p=2.65E-36; FDR=9.73E-34), compared to normal tissue. Moreover, SYNJ2BP expression was significantly reduced in advanced stages and grades (III and IV; p<0.001) compared to lower stages and grades (I and II). Decreased expression was associated with nodal invasion and metastasis (p<0.0001), unresponsive to treatment (p=0.0052), post-treatment recurrence (p=0.002), lower median overall survival (HR=0.39, 95% CI=0.28-0.54, p<0.0001), disease-specific survival (HR=0.16, 95% CI=0.09-0.27, p<0.0001) and shorter progression-free survival (HR=0.24, 95% CI=0.17-0.35, p<0.0001). Survival trends remained consistent in multivariate Cox regression, where expression remained independently associated with outcome. Consistent with transcript-level findings, immunohistochemistry demonstrated reduced protein expression of SYNJ2BP in ccRCC patients (p<0.05).
Conclusion:
SYNJ2BP is a novel prognostic biomarker for ccRCC and the down-regulation of SYNJ2BP expression is associated with poor survival outcomes and reduced treatment response.
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