Presentation Authors: Jacob W. Greenberg, Amanda Raines, M.D*, Stephen Proctor, M.D, Ibifiri Wilcox, Jonathan L. Silberstein, M.D, FACS, L. Spencer Krane M.D, New Orleans, LA
Introduction: Renal Cell Carcinoma is newly diagnosed in 58,000 individuals in the United States annually. Papillary Renal Cell Carcinoma (pRCC) is the second most common variant of renal cell carcinoma accounting for approximately 15% of these cases. Currently, there are no widely adopted biomarkers that predict patient outcomes with pRCC. The aim of this study is to create a diagnostic score based on identified miRNA signatures that could be used predict patient survival.
Methods: Patient&[prime]s clinical data and level 3 miRNA expression profiles was obtained from the Cancer Genome Atlas (TCGA) repository, an NIH funded open genomic database. Clinical data was correlated with miRNA expression data, and regression analysis Kaplan-Meier curves and Heatmap clustering were performed using R packages ComplexHeatmap and Survival regression. Statistical analysis was also performed using R Studio v3.4.4. Significant miRNAs were isolated and a diagnostic high and low score was created correlating to a miRNA expression levels.
Results: A total of 276 patients were identified who met inclusion criteria and included in this study. Two miRNAs, hsa-mir-335 and has-mir-5010, were identified using regression analysis to be most associated with overall survival. Clustering analysis produced 213 patients with a high score and 63 patients with a low score. Patients with a low score showed a significant decrease in survival(p < 0.0001) (Figure 1). This was validated in multivariate analysis with known risk factors.
Conclusions: We have created a novel miRNA signature to predict survival in pRCC using previously unreported miRNA biomarkers. hsa-mir-335 has been identified in gastric cancer as biomarker and is upstream chromosome 7q from MET, a well-known amplified gene in pRCC. hsa-mir-5010 has been used a biomarker in colon cancer but has no validated targets currently. Prospective validation of these markers is ongoing along with further determination of mir-5010 role in disease progression in underway.