MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer

• Published in: Microbial pathogenesis Vol. 149; p. 104442
• Main Authors: Schaalan, Mona, Mohamed, Waleed, Fathy, Shimaa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2020
• Subjects: biomarkers; Biomarkers, Tumor - genetics; blood serum; Case-Control Studies; complications (disease); Egypt; fibroblast growth factor receptor 2; Gastric cancer; gastrointestinal endoscopy; H. pylori-peptic ulcer; hospitals; Humans; immune response; interferon-gamma; LncRNA H19; microRNA; MicroRNAs - genetics; miR-139; miR-200c; non-coding RNA; pathogenesis; patients; quantitative polymerase chain reaction; RNA, Long Noncoding - genetics; stomach neoplasms; Stomach Neoplasms - genetics; Stomach Ulcer - genetics; stomach ulcers; tumor necrosis factor-alpha; Egypt; LncRNA H19; miR-139; H. pylori-peptic ulcer; miR-200c; Gastric cancer
• ISSN: 0882-4010; 1096-1208; 1096-1208
• DOI: 10.1016/j.micpath.2020.104442

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. 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. •This study is a case-control study assessing the expression levels of serum miR-200c, miR-139 and Ln RNA H19 in treated peptic ulcer patients vs those who progressed to gastric cancer.•The signaling mediators that are expected to be targeted by the ncRNAs are FGF-18, that is affected by Ln H19, added to BCL2 and MMPs, both have a potential regulatory role on miR-139.•The NF-κB –MEK/ ERK pathway is targeted by LnH19, while ROS and TNF-α are impacted by miR-200c.•Moreover, the correlation of the aforementioned markers with the studied ncRNAs and their predictive and prognostic value in the progression of H pylori peptic ulcer to gastric cancer have been studied.