Department of Chemistry, Kasr El Aini Teaching Hospital, Cairo University, Cairo, Egypt.
Department of Clinical Pharmacy and Pharmacy Practice, Clinical and Translational Research Unit, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
J Cell Biochem. 2019 Aug;120(8):13464-13477. doi: 10.1002/jcb.28620. Epub 2019 Apr 4.
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.
非编码 RNA、微小 RNA（miRNA）和长非编码 RNA（lncRNA）的失调与胃癌（GC）的发生和发展有关。本研究是在 75 名受试者中进行的一项初步病例对照研究，其中 40 名受试者为幽门螺杆菌胃溃疡患者，35 名受试者为埃及开罗大学 Al-Kasr Al-Aini 医院胃肠内镜科的 GC 患者。通过实时 PCR 评估血清 miR-204、miR-182 和 lncRNA H19 在进展性 GC 与非进展性消化性溃疡患者中的表达水平。评估成纤维细胞生长因子 18（FGF-18）/成纤维细胞生长因子受体 2（FGFR2）表达及其下游免疫和炎症信号标志物，并研究其与所关注非编码 RNA 的关系。关于 miR-204 和 miR-182，它们在 GU 样本中分别显著增加（分别增加 12.5 倍和 2.6 倍），高于健康对照组水平。与 GU 相比，GC 样本中这些 miRNA 的水平显著降低，miR-204 的降低倍数为 2.2 倍，miR-182 的降低倍数为 1.8 倍。另一方面，GU 中 lncRNA H19 水平的显著升高记录为 16.6 倍，其水平在 GC 样本中进一步升高。评估的 miRNAs 与疾病持续时间相关，而 miR-182 与所有炎症标志物、TAC、INF-γ、基质金属蛋白酶 9 和 FGF-18 显著相关。就评估的 miRNAs 的诊断准确性（III 期至 IV 期）而言，受试者工作特征分析表明，血清 lncRNA H19 显示出最高的诊断准确性（95.5%）、特异性（100%）和敏感性（90.9%），与 miR-204 和 miR-182 相比，特异性（60%）、敏感性（72.7%）和诊断准确性（68.8%）相同。我们的研究结果得出结论，lncRNA H19、miR-204 和 miR-182 可能作为新型潜在的血浆生物标志物，用于检测 GC 及其从幽门螺杆菌消化性溃疡的进展，这将有助于改善 GC 的治疗效果。
