title: Urinary ADAM12 and MMP-9/NGAL complex detect the presence of gastric cancer.
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.
authors.affiliation: Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts. Department of Surgery, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Takaya
authors.initials: T
authors.lastname: Shimura
authors.affiliation: Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Adelle
authors.initials: A
authors.lastname: Dagher
authors.affiliation: Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Monisha
authors.initials: M
authors.lastname: Sachdev
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Ebi
authors.affiliation: Okazaki Public Health Center, Okazaki, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
authors.affiliation: Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts. Department of Surgery, Harvard Medical School and Boston Children's Hospital, Boston, Massachusetts. marsha.moses@childrens.harvard.edu.
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Moses
mesh_terms: D051722:ADAM Proteins / Q000652:urine*; D000072199:ADAM12 Protein; D000209:Acute-Phase Proteins / Q000652:urine*; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D008565:Membrane Proteins / Q000652:urine*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D040081:Protein Array Analysis; D011518:Proto-Oncogene Proteins / Q000652:urine*; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000652:urine; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9