STRA6 Expression Serves as a Prognostic Biomarker of Gastric Cancer

Abstract

Background: Despite advances in our understanding on the pathogenesis of gastric cancer (GC), patients face a poor prognosis. To improve clinical outcomes, effective approaches to diagnosis and treatment employing new diagnostic biomarkers are required to achieve early detection and predict recurrence and prognosis.

Materials and methods: Transcriptome analysis was conducted using surgically resected gastric tissues from four patients with metastatic GC. A total of 228 pairs of primary GC tissues and corresponding normal adjacent tissues were subjected to mRNA expression analysis. To validate our findings, we accessed an integrated microarray dataset and RNA sequencing data of GC cell lines.

Results: We identified stimulated by retinoic acid 6 (STRA6) as a differentially overexpressed gene, which encodes a transmembrane protein that mediates the cellular uptake of retinol. To investigate how STRA6 contributes to the malignant phenotype of GC cells, we mined public datasets and found the mRNA encoding retinol binding protein 1 (RBP1), which is associated with retinoid metabolism, was co-expressed with STRA6. Furthermore, STRA6 mRNA levels were significantly higher in GC tissues compared to the corresponding noncancerous adjacent tissues of 228 surgically resected gastric tissue samples. Moreover, patients with high levels of STRA6 mRNA experienced significantly shorter disease-free survival and overall survival. Multivariate analysis revealed that high levels of STRA6 served as a significant risk factor.

Conclusion: Patients with high levels of STRA6 mRNA experienced significantly worse clinical outcomes, indicating that STRA6 may serve as a diagnostic and prognostic biomarker of GC.

Keywords: Gastric cancer; STRA6; biomarker; prognosis; recurrence.

Figure 1. STRA6 mRNA expression in clinical samples and survival analysis. (A) Comparison of STRA6 mRNA levels in normal adjacent tissues and GC tissues according to UICC stage,. *p<0.05. (B) Kaplan–Meier analysis of disease-free survival (DFS) and overall survival (OS) in the institutional cohort. The analyses included 228 patients who underwent curative gastrectomy for stages I-III GC. (C) Kaplan–Meier analysis of OS in the external validation cohort. OS analysis included 444 patients who underwent curative gastrectomy for stages I-III GC.

Figure 2. Frequencies of initial recurrence after curative gastrectomy in patients according to STRA6 mRNA levels. *p<0.05.