Overexpression of endothelial cell specific molecule-1 (ESM-1) in gastric cancer.
BACKGROUND
The endothelial cell-specific molecule-1 (ESM-1) gene is involved in various biological events. This study was designed to clarify its clinical significance and explore its biological behavior in gastric cancer (GC).


METHODS
ESM-1 mRNA expression was evaluated by real-time PCR in GC (n = 34) and matched adjacent normal tissues (n = 14). The expression of ESM-1 protein was investigated by immunohistochemistry in GC (n = 159) and matched normal tissues (n = 40), and its correlation with the clinicopathological features and overall survival of patients was analyzed. Microvessel density (MVD) in GC was assessed by anti-CD34 and the pattern of ESM-1 expression in tumor-related vascular was evaluated. The effect of ESM-1 promotion of proliferation in the GC MKN28 cell line and human microvascular endothelial cell line HMEC-1 were tested using the MTT assay.


RESULTS
ESM-1 mRNA was significantly overexpressed in GC compared with adjacent noncarcinoma controls (P < 0.01). ESM-1 protein was predominantly expressed in GC. ESM-1 expression was associated with distant metastasis and Borrmann type IV (P < 0.05) and was strongly associated with vascular invasion (P = 0.0057). Patients with ESM-1 expression showed lower 5-year survival rate (P = 0.0339). Multivariate analysis revealed that ESM-1 was an independent prognostic factor. In GC, CD34-MVD of GC vessels positively expressing ESM-1 was higher than that of GC with negative vessels expression of ESM-1 (P < 0.05). Besides, ESM-1 antibody dose-dependently impaired MKN28 and HMEC-1 growth.


CONCLUSIONS
ESM-1 is overexpressed in GC and can serve as a tumor biomarker to predict survival of GC patients, and it might promote tumor angiogenesis and growth in GC and, hence, may represent a potential therapeutic target.
Liu
Ni
N
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Beijing, China.
Zhang
Lian-hai
LH
Du
Hong
H
Hu
Ying
Y
Zhang
Gui-guo
GG
Wang
Xiao-hong
XH
Li
Ji-you
JY
Ji
Jia-fu
JF
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D011379:Prognosis; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D015854:Up-Regulation
C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering