Journal
MEDICAL SCIENCE MONITOR
Volume 25, Issue -, Pages 7770-7783Publisher
INT SCIENTIFIC INFORMATION, INC
DOI: 10.12659/MSM.918486
Keywords
Biological Markers; Exosomes; Matrix Metalloproteinase 14; RNA, Messenger; Stomach Neoplasms
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Funding
- National Natural Science Foundation of China [81572070, 31500741]
- Natural Science Foundation of Shandong Province [BS2014SW022, ZR2016HM37]
- Key Research and Development Project of Shandong Province [2016GSF201124, 2015GSF118152]
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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/Methods: The expression of exosomal MT1-MMP mRNA in serum of patients with GC, chronic gastritis, or atypical hyper-plasia, 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 high- er 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 se- rum exosomes-targeted biomarkers for GC diagnosis.
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