Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University Research Institute (MASRI), Abbassia, Cairo 11381, Egypt.
Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El -Aini Street, Cairo 11562, Egypt.
Urol Oncol. 2019 Apr;37(4):292.e19-292.e27. doi: 10.1016/j.urolonc.2018.12.024. Epub 2019 Jan 14.
To assist in the diagnosis, treatment, and prognostic prediction of bladder cancer, the molecular patterns associated with it should be elucidated. Competing endogenous RNA network: MicroRNA (miRNA), long noncoding RNA (lncRNA), and their target autophagy genes have been strongly implicated in tumor development and metastasis.
Bioinformatics analysis was performed to retrieve a ceRNA: lncRNA-miRNA-mRNA network linked to autophagy and relevant to bladder cancer. Expression of selected noncoding human RNAs (miR-324-5p, miR-4738-3p, and lncRNA miR-497-HG) and their target genes (RCAN1 mRNA and FOSB mRNA) was examined by qPCR in bladder tissues and urine samples obtained from 196 individuals (98 patients with bladder cancer, 48 patients with benign lesions, and 50 healthy controls).
Expression levels of the selected genes in urine samples in the bladder cancer group were significantly different from those in the control group (P < 0.001). Expression in bladder cancer tissue samples correlated with that in urine samples. Urinary expression levels of all biomarkers had high accuracy to distinguish patients with and without bladder cancer, with FOSB mRNA and RCAN1 mRNA having the highest accuracy (99% for RCAN1 mRNA or FOSB mRNA, 87.8% for miR-324-5p, 84.7% for miR-4738-3p, and 90.5% for lncRNA miR-497-HG). FOSB mRNA and RCAN1 mRNA expression showed also a higher accuracy than cytology (77.6%).
The significant differential expression of the ceRNA network: lncRNA-miRNA-mRNA network in bladder cancer as compared to noncancerous controls has revealed the superior accuracy of the chosen biomarkers to cytology, especially FOSB mRNA and RCAN1 mRNA, suggesting their involvement in bladder cancer pathogenesis and promising role for future diagnosis, and targeted therapy.
为了协助膀胱癌的诊断、治疗和预后预测，应阐明与之相关的分子模式。竞争内源性 RNA 网络：微 RNA（miRNA）、长非编码 RNA（lncRNA）及其靶自噬基因强烈参与肿瘤的发生和转移。
采用生物信息学分析方法，检索与自噬相关并与膀胱癌相关的 ceRNA：lncRNA-miRNA-mRNA 网络。通过 qPCR 检测 196 例个体（98 例膀胱癌患者、48 例良性病变患者和 50 例健康对照者）的膀胱组织和尿液中选定非编码人 RNA（miR-324-5p、miR-4738-3p 和 lncRNA miR-497-HG）及其靶基因（RCAN1 mRNA 和 FOSB mRNA）的表达。
膀胱癌组尿液样本中选定基因的表达水平与对照组相比差异有统计学意义（P<0.001）。膀胱癌组织样本中的表达与尿液样本中的表达相关。所有生物标志物在区分膀胱癌患者和非膀胱癌患者方面具有较高的准确性，其中 FOSB mRNA 和 RCAN1 mRNA 的准确性最高（RCAN1 mRNA 或 FOSB mRNA 的准确率为 99%，miR-324-5p 的准确率为 87.8%，miR-4738-3p 的准确率为 84.7%，lncRNA miR-497-HG 的准确率为 90.5%）。FOSB mRNA 和 RCAN1 mRNA 的表达也优于细胞学（77.6%）。
与非癌对照相比，膀胱癌中 ceRNA 网络：lncRNA-miRNA-mRNA 网络的显著差异表达揭示了所选生物标志物较细胞学具有更高的准确性，尤其是 FOSB mRNA 和 RCAN1 mRNA，提示其参与膀胱癌的发病机制，并有望用于未来的诊断和靶向治疗。
