Syntaxin 6: A novel predictive and prognostic biomarker in papillary renal cell carcinoma

Taylor C Peak,Gagan Deep,Yixin Su,Jacqueline Chyr,Andrew G Chapple

doi:10.1038/s41598-019-39305-z

Abstract

Syntaxin 6 is a SNARE family protein known to play an important role in intracellular trafficking. Here, we examined the tumorogenic role of syntaxin 6 in renal cell carcinoma (RCC). The Cancer Genome Atlas (TCGA) was queried for clinicopathologic data and syntaxin 6 expression. We found a significant difference in overall survival (OS) between groups, with high syntaxin 6 expression correlating with decreased survival. When stratifying the data based on histological subtype, the papillary RCC subtype exhibited a significant correlation between syntaxin 6 expression and survival. Using ROC curve, we calculated the area under the curve (AUC) to determine the ability of syntaxin 6 to predict 3-year overall survival. The AUC for syntaxin 6 was 0.73, significantly higher compared to 0.52 for T stage. Next, syntaxin 6 expression was evaluated in clear cell (786-O and Caki-1) and papillary (Caki-2 and ACHN) RCC cells. Syntaxin 6 expression was higher in Caki-1 and ACHN RCC cells. Silencing of syntaxin 6 in ACHN cells significantly decreased the cell viability (p < 0.001). Overall, syntaxin 6 could be a prognostic biomarker for patients with papillary RCC and syntaxin 6 inhibitors hold promise as a novel therapy against RCC.

Highlights

Renal cell carcinoma (RCC) has the highest mortality of all urologic malignancies
Mutations in the von Hippel-Lindau (VHL) gene prevents ubiquitination and degradation of hypoxia-inducible factors (HIF) such as HIF-1α3. This in turn leads to increased expression of vascular endothelial growth factor (VEGF), and resulting angiogenesis, as well as tumor formation and progression. pRCC and chRCC subtypes have been studied to a lesser extent, and what we do know is based largely on familial forms of the disease[3,4]
Because of the differences in disease progression based on the histologic subtypes of renal cell carcinoma (RCC), we decided to stratify the dataset based on the three most common subtypes, ccRCC, pRCC, and chRCC

Summary

Introduction

Renal cell carcinoma (RCC) has the highest mortality of all urologic malignancies. In 2017, 63,990 individuals developed RCC, and about 14,400 died due to this malignancy[1]. Of the three major histologic subtypes of RCC, 70–80% of tumors are ccRCC, 10–20% are pRCC, and 5–10% are chRCC. Mutations in the von Hippel-Lindau (VHL) gene prevents ubiquitination and degradation of hypoxia-inducible factors (HIF) such as HIF-1α3. This in turn leads to increased expression of vascular endothelial growth factor (VEGF), and resulting angiogenesis, as well as tumor formation and progression. Many of the therapies developed to treat advanced RCC have been based on disrupting the known pathways of ccRCC5. We set out to determine syntaxin 6 role in predicting oncologic outcomes in those patients with RCC, as well as its therapeutic value as a targetable protein

Methods

Results

Conclusion