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

Abstract

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.

Long Noncoding RNA and Epithelial Mesenchymal Transition in Cancer

“…The serum levels of lncRNA H19, together with miR-204, miR-182 were recently proposed as prospective plasma biomarkers to detect GC and its progression from ulcer caused by H. pylori . The authors indeed showed that serum lncRNA H19 has a high diagnostic accuracy, specificity and sensitivity [146]. Another work, on bladder cancer (BC), showed a positive correlation among serum exosomal H19 with total H19 level in paired cancer tissues.…”

The prognostic value of COL3A1/FBN1/COL5A2/SPARC-mir-29a-3p-H19 associated ceRNA network in Gastric Cancer through bioinformatic exploration

“…Based on TCGA data, integrating expression analysis and survival analysis of these lncRNAs, only 1 lncRNA (H19) was considered as the central lncRNA. Moreover, overexpression of lncRNA H19 has been determined to enhance the proliferation, invasion of gastric cancer and contributed to poor prognosis in GC patients in multiple studies 46 - 49 . Naturally, a prognosis-related mRNA-miRNA-lncRNA ceRNA network in gastric cancer was successfully constructed.…”

Review: Helicobacter pylori and non‐malignant upper gastrointestinal diseases

“…Predictive biomarkers for PUD are also under evaluation. In a case‐control study, Mohamed et al examined the use of microRNAs, non‐coding RNAs, and long non‐coding RNAs as biomarkers to detect gastric cancer and its progression from H pylori ‐induced PUD . lncRNA H19, miR‐204, and miR‐182 were identified as potential plasma biomarkers to detect progression to gastric cancer in patients with PUD.…”