Mona Schaalan1, Waleed Mohamed2, Shimaa Fathy3. 1. Department of Clinical Pharmacy, Clinical and Translational Research Unit, Faculty of Pharmacy, Misr International University, Cairo, Egypt. Electronic address: Mona.Schaalan@miuegypt.edu.eg. 2. Department of Internal Medicine, Kasr El Aini Teaching Hospitals, Cairo University, Cairo, Egypt. Electronic address: waleedalilab@yahoo.com. 3. Department of Clinical Pharmacy, Clinical and Translational Research Unit, Faculty of Pharmacy, Misr International University, Cairo, Egypt. Electronic address: shery.fathy@miuegypt.edu.eg.
Abstract
Recent evidence indicates that the pathogenesis of gastric ulcer and progression to gastric cancer could be attributed to altered inflammatory/immunological response and associated differential non-coding RNAs expression signatures. However, co-expression profiling of lncRNA-miRNAs in GU/GC patients are scarcely focused on. Therefore, in the present study the expression of H19 and related miRNAs including miR-139, and miR-200 were assayed in the plasma samples of treatment responsive GU vs nonresponsive GC patients. This study is a case-control study carried out on 130 subjects recruited from the Gastrointestinal Endoscopy Unit in Al-Kasr Al-Aini Hospital, in Egypt. All recruited patients were diagnosed with H-pylori infection, 50 of them were gastric cancer patients (GC), with previous H-pylori induced gastric ulcer but were treatment non-respondent. Real-time PCR was performed to evaluate the expression level of serum non-coding RNA; miRNA-200c, miR-139, Ln RNA H19 in patients with peptic ulcer treatment non-respondent, who progressed to GC vs non-progressed gastric ulcer patients (GU) (n = 50), and compared to early diagnosed H-pylori-gastric ulcer patients (n = 30). The association between these miRNAs and the FGF-18/FGF-R signaling indicators of H-pylori-GC pathogenesis were then investigated. RESULTS: showed that the H19 level was significantly elevated while miR-139 and miR-200c expression were significantly down-regulated in GC patients, compared to GU participants (P < 0.01). The herein investigated ncRNAs are correlated to the disease duration with Ln H19 being significantly correlated with all inflammatory markers; TNF-α, INF-γ, TAC, MMP-9, and FGF18/FGFR2. A significant correlation was also observed between miRNA 200c and each of miRNA 139 and FGFR2. Moreover, ROC analysis revealed that miRNA 200c showed the highest AUC (0.906) and 81.2% sensitivity and 100% specificity. Moreover, the combined analysis of miRNA 200c/miRNA 139 revealed superior AUC (0.96) and 93% sensitivity and 100% specificity, than each separately. As for discriminative accuracy between stages III to IV of gastric cancer, LncRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%). The current study demonstrated that the combination of serum miRNA 200c/miRNA 139 expression levels (down-regulation) could provide a new potential prognostic panel for GU predictive response and potential sequelae. In conclusion, LncRNA H19 and related miRNAs, miRNA 200c/miRNA 139, could serve as a potential diagnostic biomarker for early gastric cancer diagnosis.
Recent evidence indicates that the pathogenesis of gastric ulcer and progression to gastric cancer could be attributed to altered inflammatory/immunological response and associated differential non-coding RNAs expression signatures. However, co-expression profiling of lncRNA-miRNAs in GU/GC patients are scarcely focused on. Therefore, in the present study the expression of H19 and related miRNAs including miR-139, and miR-200 were assayed in the plasma samples of treatment responsive GU vs nonresponsive GC patients. This study is a case-control study carried out on 130 subjects recruited from the Gastrointestinal Endoscopy Unit in Al-Kasr Al-Aini Hospital, in Egypt. All recruited patients were diagnosed with H-pylori infection, 50 of them were gastric cancer patients (GC), with previous H-pylori induced gastric ulcer but were treatment non-respondent. Real-time PCR was performed to evaluate the expression level of serum non-coding RNA; miRNA-200c, miR-139, Ln RNA H19 in patients with peptic ulcer treatment non-respondent, who progressed to GC vs non-progressed gastric ulcer patients (GU) (n = 50), and compared to early diagnosed H-pylori-gastric ulcer patients (n = 30). The association between these miRNAs and the FGF-18/FGF-R signaling indicators of H-pylori-GC pathogenesis were then investigated. RESULTS: showed that the H19 level was significantly elevated while miR-139 and miR-200c expression were significantly down-regulated in GC patients, compared to GU participants (P < 0.01). The herein investigated ncRNAs are correlated to the disease duration with Ln H19 being significantly correlated with all inflammatory markers; TNF-α, INF-γ, TAC, MMP-9, and FGF18/FGFR2. A significant correlation was also observed between miRNA 200c and each of miRNA 139 and FGFR2. Moreover, ROC analysis revealed that miRNA 200c showed the highest AUC (0.906) and 81.2% sensitivity and 100% specificity. Moreover, the combined analysis of miRNA 200c/miRNA 139 revealed superior AUC (0.96) and 93% sensitivity and 100% specificity, than each separately. As for discriminative accuracy between stages III to IV of gastric cancer, LncRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%). The current study demonstrated that the combination of serum miRNA 200c/miRNA 139 expression levels (down-regulation) could provide a new potential prognostic panel for GU predictive response and potential sequelae. In conclusion, LncRNA H19 and related miRNAs, miRNA 200c/miRNA 139, could serve as a potential diagnostic biomarker for early gastric cancer diagnosis.