Abstract
BackgroundNoggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear.MethodsA total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed.ResultsRBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P < 0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P < 0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35–0.97, P < 0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81–2.26, P = 0.251).ConclusionsOur study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.
Highlights
Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts
To identify the molecular pathways enriched in the co-expressed stroma-related genes, NOGGIN and RBPMS2, we conducted Gene Set Enrichment Analysis (GSEA) for KEGG pathways and identified the enriched pathways (Supplementary Fig. 1)
We found that low Noggin protein expression at the invasive front of gastric cancer (GC) was more frequent in the group at an advanced T stage and in the non-intestinal Lauren’s subtype, suggesting that the high Noggin expression was associated with a favorable clinical outcome in patients with resected GC
Summary
Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. The prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. Early diagnosis and the development of surgical techniques have led to a significant improvement in clinical outcomes of patients with resectable GC. The 5-year survival rate of patients with early GC is over 90% [2]. Despite remarkable advances in targeted therapy for molecular targets, vascular endothelial growth factor receptor (VEGFR), and human epidermal growth factor receptor 2 (HER2) to improve patient survival in the setting of recurrent and metastatic GC, the prognosis of patients with recurrent and metastatic GC remains poor [3]. New molecular therapeutic targets and biomarkers are required to improve the survival of patients with GC. Tumor-stroma interaction at the invasive front of the tumor represents a critical interface, where tumor progression and tumor cell dissemination occur due to the lack of cohesiveness, secretion of proteolytic enzymes, re-organization of the ECM, and increased cell proliferation [5]
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