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Urinary ADAM12 and MMP-9/NGAL Complex Detect the Presence of Gastric Cancer

Authors :
Takashi Joh
Takaya Shimura
Marsha A. Moses
Tamaki Yamada
Adelle Dagher
Tomonori Yamada
Monisha Sachdev
Masahide Ebi
Source :
Cancer Prevention Research. 8:240-248
Publication Year :
2015
Publisher :
American Association for Cancer Research (AACR), 2015.

Abstract

Although the early diagnosis of gastric cancer provides the opportunity for curative endoscopic resection, comprehensive screening endoscopy would be invasive and expensive. To date, there is a complete absence of clinically useful gastric cancer biomarkers. With the goal of discovering noninvasive biomarkers for the early diagnosis of gastric cancer, we have conducted a case–control study using urine samples from individuals with gastric cancer versus healthy control samples. Of the enrolled 106 patients from September, 2012 to April, 2013, a cohort of 70 patients composed of 35 patients with gastric cancer and 35 age- and sex-matched healthy controls was analyzed. The gastric cancer group was composed of stage IA of 62.9% (22/35). The urinary levels of MMP-9/NGAL complex (uMMP-9/NGAL) and ADAM12 (uADAM12) were significantly higher in the gastric cancer group compared with the healthy control group as determined by monospecific ELISAs (uMMP-9/NGAL: median, 85 pg/mL vs. 0 pg/mL; P = 0.020; uADAM12: median, 3.35 ng/mL vs. 1.44 ng/mL; P < 0.001). Multivariate analysis demonstrated that both uMMP-9/NGAL and uADAM12 were significant, independent diagnostic biomarkers for gastric cancer. Moreover, MMP-9/NGAL activity was significantly elevated as determined by gelatin zymography. The combination of uMMP-9/NGAL with uADAM12 distinguished between control samples and gastric cancer samples with an AUC of 0.825 (P < 0.001) in an ROC analysis. Significantly, immunohistochemical analyses demonstrated a high coexpression of MMP-9 and NGAL (P < 0.001) and high expression of ADAM12 (P < 0.001) in gastric cancer tissues compared with adjacent normal tissues (N = 35). In summary, uMMP-9/NGAL and uADAM12 are potential noninvasive biomarkers for gastric cancer, including early-stage disease. Cancer Prev Res; 8(3); 240–8. ©2015 AACR.

Details

ISSN :
19406215 and 19406207
Volume :
8
Database :
OpenAIRE
Journal :
Cancer Prevention Research
Accession number :
edsair.doi.dedup.....e30395b5fe95e8d253c08c375b7c23d1
Full Text :
https://doi.org/10.1158/1940-6207.capr-14-0229