| RRC ID |
38361
|
| 著者 |
Toiyama Y, Tanaka K, Kitajima T, Shimura T, Imaoka H, Mori K, Okigami M, Yasuda H, Okugawa Y, Saigusa S, Ohi M, Inoue Y, Mohri Y, Goel A, Kusunoki M.
|
| タイトル |
Serum angiopoietin-like protein 2 as a potential biomarker for diagnosis, early recurrence and prognosis in gastric cancer patients.
|
| ジャーナル |
Carcinogenesis
|
| 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.
|
| 巻・号 |
36(12)
|
| ページ |
1474-83
|
| 公開日 |
2015-12-1
|
| DOI |
10.1093/carcin/bgv139
|
| PII |
bgv139
|
| PMID |
26420253
|
| MeSH |
Adolescent
Adult
Aged
Aged, 80 and over
Angiopoietin-Like Protein 2
Angiopoietin-like Proteins
Angiopoietins / blood*
Angiopoietins / genetics
Anoikis
Area Under Curve
Biomarkers, Tumor / blood*
Case-Control Studies
Cell Line, Tumor
Cell Proliferation
Disease-Free Survival
Early Detection of Cancer
Female
Gene Expression
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Neoplasm Recurrence, Local / blood*
Neoplasm Recurrence, Local / diagnosis
Prognosis
Proportional Hazards Models
ROC Curve
Stomach Neoplasms / blood*
Stomach Neoplasms / diagnosis
Stomach Neoplasms / mortality
Young Adult
|
| IF |
4.603
|
| 引用数 |
20
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MKN1(RCB1003)
MKN7(RCB0999)
MKN45(RCB1001)
MKN74(RCB1002)
Kato III(RCB2088)
NUGC-4(RCB1939) |
