Abstract
Cell plasma membrane proteins, playing a crucial role in cell malignant transformation and development, were the main targets of tumor detection and therapy. In this study, CyDye/biotin double-labeling proteomic approach was adopted to profile the membrane proteome of gastric cancer cell line BGC-823 and paired immortalized gastric epithelial cell GES-1. Real-time PCR, Western blotting, and immunohistochemical staining were used to validate the differential expression of a novel identified cell surface marker R-cadherin in gastric cancer cells and tissues. Clinicopathological study and survival analysis were performed to estimate its roles in tumor progression and outcome prediction. Real-time PCR and Western blotting showed that the expression level of R-cadherin in gastric cancer were significantly lower than non-cancerous epithelial cell and tissues. Clinicopathological study indicated that R-cadherin was dominantly expressed on cell surface of normal gastric epithelium, and its expression deletion in gastric cancer tissues was associated with tumor site, differentiation, lymph node metastasis, and pTNM (chi-square test, P < 0.05). Those patients with R-cadherin positive expression displayed better overall survivals than negative expression group (log-rank test, P = 0.000). Cox multivariate survival analysis revealed lacking the expression of R-cadherin was a main independent predictor for poor clinical outcome in gastric cancer (RR = 5.680, 95 % CI 2.250–14.341, P < 0.01). We have established a fundamental membrane proteome database for gastric cancer and identified R-cadherin as a tumor differentiation and progression-related cell surface marker of gastric cancer. Lacking the expression of R-cadherin indicates poor prognosis in patients with gastric cancer.
Highlights
Gastric cancer (GC) is the second most common cause of cancer death worldwide, its incidence and mortality have fallen dramatically over the last 50 years [1, 2]
Tumor staging was assessed using the seventh edition of the tumor, node, metastasis (TNM) system according to the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC)
Results from Western blotting showed the expression of Rcadherin was significantly lower in clinical GC tissues and GC cell lines, as compared to the adjacent normal mucosa to gastric carcinoma and the gastric epithelial cells, respectively (Fig. 3c–e)
Summary
Gastric cancer (GC) is the second most common cause of cancer death worldwide, its incidence and mortality have fallen dramatically over the last 50 years [1, 2]. (2016) 37:11775–11787 sensitive and specific biomarkers [7]. Screening more specific and sensitive early diagnostic biomarkers is an effective way to improve overall outcomes of GC [8, 9]. Despite significant improvements in systemic chemotherapy over the last two decades, the prognosis of advanced GC remains frustrating. As a part of comprehensive treatment for gastric carcinoma, targeted chemotherapy and its related treatment have wide development in recent years [10, 11]. Discovering new therapeutic targets is a valuable and challenging work to improve the prognosis of GC
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