Exosomal MT1-MMP mRNA in Serum As a Potential Biomarker for Gastric Cancer

Background: Our previous results reveal that membrane type 1-matrix metalloproteinase (MT1-MMP) is overexpressed and plays a crucial roles in gastric cancer (GC) progression. Exosomes are important for GC carcinogenesis, and the exosomal contents are used as ideal biomarkers. However, the expression of exosomal MT1-MMP mRNA in serum and its potential significance in GC remains unclear. Methods: The expression of exosomal MT1-MMP mRNA in serum of GC, chronic gastritis, atypical hyperplasia, and healthy controls were detected using real-time quantitative RT-PCR. Meanwhile, serum CEA, CA19-9 and CA72-4 were also measured by electrochemiluminescence assay. Findings: Exosomes were isolated and identified in serum. Our results revealed that exosomal MT1-MMP mRNA in serum was elevated in GC, compared with healthy controls, chronic gastritis, atypical hyperplasia, respectively (all P<0.05). It was significantly correlated with tumor diameter, differentiation, borrmann type, invasion depth, lymphatic metastasis, distal metastasis, TNM stage. AUC of exosomal MT1-MMP mRNA was 0.788 (95%CI: 0.714-0.850) with sensitivity 63.9% and specificity 87.1%, and higher than that of CEA (0.655 (95%CI: 0.573-0.730)). The combination of two markers gave an AUC of 0.821 (95%CI: 0.750-0.878), better than the individual marker. The sensitivity, specificity, positive and negative predictive value were 75.6%, 83.9%, 94.7%, 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 of lymphatic metastasis in GC. Interpretation: As a pilot investigation to characterizing the serum exosomal MT1-MMP mRNA in GC, our study provided a foundation for discovering serum exosomes-targeted biomarkers for GC diagnosis. Funding Statement: 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). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Our study was approved by Medical Ethics Committee of Qilu Hospital of Shandong University (KYLL-2015-097). The participants signed written informed consents.