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17 October 2019 : Clinical Research  

Serum Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) mRNA Protected by Exosomes as a Potential Biomarker for Gastric Cancer

Zhaogang Dong1ABDEG, Xiaoyan Sun2BCEF, Jingjing Xu3CF, Xia Han4BD, Zhaoquan Xing4DFG, Ding Wang1BCD, Jian Ge2DF, Liwei Meng4BC, Xiaofei Xu5ADEFG*

DOI: 10.12659/MSM.918486

Med Sci Monit 2019; 25:7770-7783

Abstract

BACKGROUND: Our previous research revealed that membrane type 1-matrix metalloproteinase (MT1-MMP) is overexpressed and plays a crucial role in gastric cancer (GC) progression. Exosomes are important for GC carcinogenesis, and the exosomal contents are ideal biomarkers. However, the expression of exosomal MT1-MMP mRNA in serum and its potential significance in GC remains unclear.

MATERIAL AND METHODS: The expression of exosomal MT1-MMP mRNA in serum of patients with GC, chronic gastritis, or atypical hyperplasia, and healthy controls was detected using real-time quantitative RT-PCR. Serum CEA, CA19-9, and CA72-4 were also measured by electrochemiluminescence assay.

RESULTS: Exosomes were isolated and identified in serum, and serum exosomal MT1-MMP mRNA was found to be higher in patients with GC compared with healthy controls and patients with chronic gastritis or atypical hyperplasia (all P<0.05). Serum exosomal MT1-MMP mRNA was significantly correlated with tumor diameter, differentiation, Borrmann type, invasion depth, lymphatic metastasis, distal metastasis, and TNM stage. The AUC of exosomal MT1-MMP mRNA was 0.788 (95% CI: 0.714–0.850) with 63.9% sensitivity and 87.1% specificity, and was higher than that of CEA (0.655 (95% CI: 0.573–0.730)). The combination of 2 markers gave an AUC of 0.821 (95% CI: 0.750–0.878), which was better than with the individual marker. The sensitivity, specificity, and positive and negative predictive values were 75.6%, 83.9%, 94.7%, and 47.3%, respectively. Moreover, the multiple logistic regression model showed that tumor diameter, differentiation, invasion depth, and exosomal MT1-MMP mRNA were the risk factors for lymphatic metastasis in GC.

CONCLUSIONS: Our results characterized serum exosomal MT1-MMP mRNA in GC, providing a foundation for discovering serum exosomes-targeted biomarkers for GC diagnosis.

Keywords: Biological Markers, exosomes, Matrix Metalloproteinase 14, RNA, Messenger, Stomach Neoplasms, Antigens, Tumor-Associated, Carbohydrate, Biomarkers, Tumor, CA-19-9 Antigen, Carcinoembryonic Antigen, Disease Progression, Lymphatic Metastasis, Middle Aged

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750