Research on clinical application value of MMP quantitative array in diagnosis of gastric cancer

Abstract

Objective To explore the clinical value of matrix metalloproteinase (MMPs) antibody chip in the diagnosis of gastric cancer (GC) . Methods Serum samples from 12 patients with gastric cancer (GC) and 10 patients with non-neoplastic gastric disease (NGD) diagnosed in our hospital from November 2016 to March 2017 were collected to form a training set. Human MMP arrays were used to quantitative measurement of 7 major secretory MMPs and 3 tissue inhibitors of metalloproteinases (TIMPs) simultaneously in the above patients. Their concentration differences between GC and NGD groups and their diagnostic efficacy for GC were compared. The MMP subtypes with the greatest concentration difference between the two groups were screened for further study. Serum samples from 40 patients with GC and 38 patients with NGD diagnosed in our hospital from April 2017 to July 2017 were collected to form a validation set. The concentration of TIMP-4 in serum of these patients was detected by suspension microbead chip. Then the levels of TIMP-4 was compared between the GC and NGD groups and its diagnostic value was assessed by ROC curve. Results The MMP subtypes with high expression (>10 000 pg/ml) in the training set included: MMP-1, MMP-3, MMP-9 and TIMP-1; medium expression (1 000-10 000 pg/ml) : MMP-8, TIMP-2 and TIMP-4; low expression (<1 000 pg/ml) : MMP-2, MMP-10 and MMP-13. Compared with the NGD group, except MMP-2, MMP-3 and MMP-13, other MMPs showed an upward trend in the GC group, but no significant difference. Only TIMP-4 increased significantly in the GC group than NGD group (P<0.05) . The area under the curve (AUC) of the MMP family members for the diagnosis of GC ranged from 0.500 to 0.858, and their combined AUC was 0.925 (95%CI: 0.782-1.000) . Particularly, TIMP-4, whose AUC was the highest, was 0.858 (95%CI: 0.692-1.000) . At the optimal cut-off value of 2 438.3 pg/ml, its sensitivity, specificity and Yoden index for the diagnosis of GC were 83.3%, 80% and 0.633, respectively. In the validation set, the concentrations of TIMP-4 in the GC and NGD groups were (1 148.0±691.5) pg/ml and (834.3±397.2) pg/ml, respectively (P<0.05) . Its AUC was 0.628 (95%CI: 0.498-0.758) . Conclusions The detection of serum MMP expression profile is expected to be a new method for assistant diagnosis and screening of GC. TIMP-4 has certain reference value for the diagnosis of GC, but its diagnostic ability needs further verification. Key words: Gastric cancer; Multiple biomarkers; Matrix metalloproteinase; Antibody array; Proteomics