1. Serum angiopoietin-like protein 2 as a potential biomarker for diagnosis, early recurrence and prognosis in gastric cancer patients
- Author
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Yasuhiro Inoue, Yuji Toiyama, Takahito Kitajima, Ajay Goel, Tadanobu Shimura, Koichiro Mori, Kouji Tanaka, Hiroki Imaoka, Hiromi Yasuda, Masaki Ohi, Susumu Saigusa, Yoshinaga Okugawa, Masato Okigami, Masato Kusunoki, and Yasuhiko Mohri
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Gene Expression ,Matched Tissues ,Inflammation ,Kaplan-Meier Estimate ,medicine.disease_cause ,Gastroenterology ,Disease-Free Survival ,Young Adult ,Stomach Neoplasms ,Cell Line, Tumor ,Internal medicine ,Biomarkers, Tumor ,medicine ,Gastric mucosa ,Humans ,Clinical significance ,Angiopoietin-Like Protein 2 ,Early Detection of Cancer ,Aged ,Cell Proliferation ,Proportional Hazards Models ,Aged, 80 and over ,business.industry ,Case-control study ,Cancer ,General Medicine ,Middle Aged ,Anoikis ,Prognosis ,medicine.disease ,Angiopoietin-like Proteins ,medicine.anatomical_structure ,ROC Curve ,Tumor progression ,Area Under Curve ,Case-Control Studies ,Multivariate Analysis ,Female ,Neoplasm Recurrence, Local ,medicine.symptom ,Carcinogenesis ,business ,Angiopoietins - Abstract
Chronic inflammation of gastric mucosa by Helicobacter pylori infection can initiate gastric carcinogenesis. As angiopoietin-like protein 2 (ANGPTL2) mediates inflammation and inflammation-associated carcinogenesis, we investigated the functional and clinical significance of ANGPTL2 in human gastric cancer (GC). SiRNA knockdown studies were performed for the functional assessment of ANGPTL2 in GC cell lines. ANGPTL2 expression was evaluated immunohistochemically in 192 tissue specimens from GC patients. In addition, we screened serum ANGPTL2 levels from 32 GC patients and 23 healthy controls; and validated these results in 194 serum samples from GC patients and 45 healthy controls by ELISA. ANGPTL2 knockdown caused anoikis and inhibited proliferation, invasion and migration in GC cells. ANGPTL2 expression was upregulated in GC tissues compared to normal gastric mucosa; and high ANGPTL2 expression was significantly associated with tumor progression, early recurrence (P = 0.003) and poor prognosis (P = 0.007). Serum ANGPTL2 in GC patients was significantly higher than for healthy controls (P < 0.05), and accurately distinguished GC patients from healthy control (AUC = 0.865). The validation step confirmed significantly higher serum ANGPTL2 levels in GC patients than healthy controls (P < 0.0001). Receiver operating characteristic curves yielded robust AUC value (0.831) accompanied by high sensitivity (73.0%) and specificity (82.2%) in distinguishing GC patients from healthy controls. High serum ANGPTL2, rather than its expression in matched tissues, was significantly associated with tumor progression, and emerged as an independent marker for recurrence (HR: 5.05, P = 0.0004) and prognosis (HR: 3.6, P = 0.01). Serum ANGPTL2 expression is a potential noninvasive biomarker for diagnosis, early recurrence and prognosis of GC patients.
- Published
- 2015