Abstract
Sorting nexin-1 (SNX1) is an important functional protein in cell endocytosis, efflux, protein sorting, cell signal transduction, etc; however, the expression, the role and clinical relevance of SNX1 have not been investigated in gastric cancer (GC). In this study, we first performed a bioinformatics investigation using the data obtained from The Cancer Genome Atlas (TCGA) database. The result showed that SNX1 mRNA levels were significantly lower in GC tissues than in paracancerous tissues. In a study of 150 cases of GC, including 60 cases with paired paracancerous and cancer tissues and 90 cases with detailed follow-up information, SNX1 expression was analyzed by immunohistochemistry. Our study on paired paracancerous and cancer tissues showed that SNX1 protein expression remarkably decreased in GC tissues (50/60, 83.33%). A study on 90 patients with detailed follow-up information showed that tumors with higher SNX1 protein level were correlated with better clinicopathologic stages (p = 0.0285), nodal status (p = 0.0286), smaller tumor sizes (p = 0.0294) and a better survival rate in patients with GC (p = 0.0245). Univariate analysis of the 90 patients with GC showed that low-level SNX1 was significantly correlated with decreased overall survival of GC patients (p = 0.008), and associated with a relatively higher cumulative hazard of death. Exogenous expression of SNX1 inhibited the growth, migration, invasion and promoted the apoptosis and enhanced the sensitivity of GC cells to the chemotherapeutic drug 5-Fluorouracil (5-Fu) in vitro, while knockdown of SNX1 by short hairpin RNA (shRNA) significantly promoted the growth, migration, invasion and reduced the apoptosis and the sensitivity of GC cells to 5-Fu. SNX1 also showed to influence the levels of epithelial-mesenchymal transition markers including Vimentin, Snail, and E-cadherin in GC cells in vitro. Taken together, we propose here that SNX1 serves as a tumor suppressor and prognostic marker that reduces tumor cell malignancy for GC.
Highlights
Gastric cancer (GC) is the fifth most common malignancy worldwide and causes the third most cancer-related death (Ferlay et al, 2015)
Quantifiable levels of Sorting nexin-1 (SNX1) in the tissues were measured by histochemistry score (H-score), which was obtained based on the proportion and intensity of brown staining cells with calculation formula: H-score = (% of cells stained at intensity 1 × 1) + (% of cells stained at intensity 2 × 2) + (% of cells stained at intensity 3 × 3) (Yeo et al, 2015)
We found differential expression of SNX1 mRNA between GC tissues and NCTs through the The Cancer Genome Atlas (TCGA) database analysis: the GC tissues had a lower level of SNX1 mRNA (t-test and paired t-test, p < 0.01, Fig. S1)
Summary
Gastric cancer (GC) is the fifth most common malignancy worldwide and causes the third most cancer-related death (Ferlay et al, 2015). How to cite this article Zhan et al (2018), Sorting nexin-1 is a candidate tumor suppressor and potential prognostic marker in gastric cancer. GC in China every year which account for nearly half of the world’s GC deaths (Sheets, 2014). Several risk factors have been identified for GC, including Helicobacter pylori infection, Epstein-Barr virus infection, and dietary factors (Carrasco & Corvalan, 2013; Chen et al, 2015; Guggenheim & Shah, 2013). The pathogenesis of GC is still quite complex numerous studies investigated molecular mechanisms of the initiation and development of GC. Investigating the pathogenesis of GC, finding new biomarkers with higher sensitivity and representability are desired
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