Serum Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) mRNA Protected by Exosomes as a Potential Biomarker for Gastric Cancer
Zhaogang Dong, Xiaoyan Sun, Jingjing Xu, Xia Han, Zhaoquan Xing, Ding Wang, Jian Ge, Liwei Meng, Xiaofei Xu
Department of Clinical Laboratory Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland)
Med Sci Monit 2019; 25:7770-7783
Available online: 2019-10-17
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