title: Efficient isolation and proteomic analysis of cell plasma membrane proteins in gastric cancer reveal a novel differentiation and progression related cell surface marker, R-cadherin.
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.
authors.affiliation: Department of Gastrointestinal Surgery, Xiamen Cancer Hospital of The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, China. chenbo7892@xmu.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Central Laboratory, Xiamen Cancer Hospital of The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, China.
authors.forename: Qi-Cong
authors.initials: QC
authors.lastname: Luo
authors.affiliation: Department of Oncology, Chenggong Hospital affiliated to Xiamen University, 361003, Xiamen, Fujian, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Xiamen Cancer Hospital of The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, China.
authors.forename: Li-E
authors.initials: LE
authors.lastname: Lin
authors.affiliation: Department of Gastrointestinal Surgery, Xiamen Cancer Hospital of The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, China.
authors.forename: Ming-Xu
authors.initials: MX
authors.lastname: Luo
authors.affiliation: Department of Biobank, Xiamen Cancer Hospital of The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, China.
authors.forename: Hong-Yue
authors.initials: HY
authors.lastname: Ren
authors.affiliation: Department of Pathology, Xiamen Cancer Hospital of The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, China.
authors.forename: Pei-Qiong
authors.initials: PQ
authors.lastname: Chen
authors.affiliation: Department of Pathology, Xiamen Cancer Hospital of The First Affiliated Hospital of Xiamen University, 361003, Xiamen, Fujian, China.
authors.forename: Lian-Guo
authors.initials: LG
authors.lastname: Shi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D020543:Proteome / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D008565:Membrane Proteins; D020543:Proteome; C083970:R-cadherin
keywords: Cell surface proteins; Gastric adenocarcinoma; R-cadherin; Tumor biomarker; Tumor differentiation; Tumor progression