The expression profiling of circulating miR‐204, miR‐182, and lncRNA H19 as novel potential biomarkers for the progression of peptic ulcer to gastric cancer

• Published in: Journal of cellular biochemistry Vol. 120; no. 8; pp. 13464 - 13477
• Main Authors: Mohamed, Waleed A., Schaalan, Mona F., Ramadan, Basma
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2019
• Subjects: Accuracy; Biomarkers; Cancer; Deregulation; Diagnostic systems; Endoscopy; Fibroblast growth factor 18; Fibroblast growth factor receptor 2; Gastric cancer; gastric cancer H. pylori‐peptic ulcer; Growth factors; Helicobacter pylori; Immunology; Inflammation; lncRNA; Matrix metalloproteinases; Metalloproteinase; miRNA; miR‐204, miR‐182; Precision medicine; Sensitivity; Ulcers; miR-204, miR-182; lncRNA; gastric cancer H. pylori-peptic ulcer
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.28620

Deregulation of noncoding RNAs, microRNAs (miRNAs) and long noncoding RNA (lncRNA), are implicated in the initiation and progression of gastric cancer (GC). This study is a pilot case‐control study carried out on 75 subjects, 40 of them were Helicobacter pylori‐gastric ulcer patients and 35 were GC patients recruited from the Gastrointestinal Endoscopy Unit in Al‐Kasr Al‐Aini Hospital, Cairo University in Egypt. Real‐time PCR was performed to evaluate the expression level of serum miR‐204, miR‐182, and lncRNA H19 in patients with peptic ulcer‐progressed GC vs nonprogressed peptic ulcer patients. Fibroblast growth factor 18 (FGF‐18)/FGF receptor 2 (FGFR2) expression and their downstream immunological and inflammatory signaling markers were assessed and their association with the addressed noncoding RNAs investigated. As regards miR‐204 and miR‐182, they were significantly increased (12.5 and 2.6 folds, respectively) in GU samples, compared with those of healthy control levels. The elevated levels of these miRNAs were significantly de‐escalated in GC samples compared with GU and the fold decrease valued 2.2 fold for miR‐204 and 1.8 folds for miR‐182. On the other hand, the significant escalation in the level of lnRNA H19 in GU recorded a 16.6 fold increase and further elevation in its levels was evident in GC samples. The herein assessed miRNAs are correlated with disease duration and FGFR2 with miR‐182 being significantly correlated with all inflammatory markers, TAC, INF‐γ, matrix metallopeptidase 9, and FGF‐18. In terms of diagnostic accuracy of assessed miRNAs (stages III to IV), the receiver operating characteristic analysis indicated that serum lncRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%), compared with miR‐204 and miR‐182, which showed the same specificity (60%), sensitivity (72.7%), and diagnostic accuracy (68.8%). Our findings conclude that lnRNA H19, miR‐204, and miR‐182 may function as novel prospective plasma biomarkers to detect GC and its progression from H. pylori‐peptic ulcer, which would be helpful to improve the theranostics of GC. This study is a case‐control study aiming to evaluate the expression level of serum miR‐204, miR‐182, and long noncoding RNA (lncRNA) H19 in patients with peptic ulcer‐progressed gastric cancer (GC) (35) vs nonprogressed peptic ulcer patients (40). As regards the selected noncoding RNAs, miR‐204 and miR‐182, they all were significantly increased in GU samples compared with healthy control levels and the levels of increase were 12.5 and 2.6 folds, respectively. The elevated levels of these microRNAs (miRNAs) were significantly de‐escalatd in GC samples compared with GU and the fold decrease valued (2.2‐1.8 folds). On the other hand, the significant escalation in the level of lnRNA H19 in GU was a 16.6 fold increase and further elevation in its levels was evident in GC samples. The herein assessed miRNAs are correlated with disease duration and fibroblast growth factor receptor 2, with miR‐182 being significantly correlated with all inflammatory markers; TAC, INF‐γ, matrix metallopeptidase 9, fibroblast growth factor 18. In terms of the diagnostic accuracy of assessed miRNAs (stages III to IV), the receiver operating characteristic analysis indicated that serum lnRNA H19 showed the highest diagnostic accuracy (95.5%), specificity (100%), and sensitivity (90.9%), compared with miR‐204, and miR‐182, which showed the same specificity (60%), sensitivity (72.7%), and diagnostic accuracy (68.8%).