Laboratory of Medical Investigation, Urology Department, University of São Paulo Medical School, São Paulo, Brazil.
J Urol. 2012 Nov;188(5):1951-6. doi: 10.1016/j.juro.2012.07.004. Epub 2012 Sep 20.
We identified miRNA expression profiles in urothelial carcinoma that are associated with grade, stage, and recurrence-free and disease specific survival.
The expression of 14 miRNAs was evaluated by quantitative reverse transcriptase-polymerase chain reaction in surgical specimens from 30 patients with low grade, noninvasive (pTa) and 30 with high grade, invasive (pT2-3) urothelial carcinoma. Controls were normal bladder tissue from 5 patients who underwent surgical treatment for benign prostatic hyperplasia. Endogenous controls were RNU-43 and RNU-48. miRNA profiles were compared and Kaplan-Meier curves were constructed to analyze disease-free and disease specific survival.
miR-100 was under expressed in 100% of low grade pTa specimens (p <0.001) and miR-10a was over expressed in 73.3% (p <0.001). miR-21 and miR-205 were over expressed in high grade pT2-3 disease (p = 0.02 and <0.001, respectively). The other miRNAs were present at levels similar to those of normal bladder tissue or under expressed in each tumor group. miR-21 over expression (greater than 1.08) was related to shorter disease-free survival in patients with low grade pTa urothelial carcinoma. Higher miR-10a levels (greater than 2.30) were associated with shorter disease-free and disease specific survival in patients with high grade pT2-3 urothelial carcinoma.
Four miRNAs were differentially expressed in the 2 urothelial carcinoma groups. miR-100 and miR-10a showed under expression and over expression, respectively, in low grade pTa tumors. miR-21 and miR-205 were over expressed in pT2-3 disease. In addition, miR-10a and miR-21 over expression was associated with shorter disease-free and disease specific survival. miRNAs could be incorporated into the urothelial carcinoma molecular pathway. These miRNAs could also serve as new diagnostic or prognostic markers and new target drugs.
我们鉴定了与膀胱癌分级、分期、无复发生存和疾病特异性生存相关的尿路上皮癌中的 miRNA 表达谱。
通过定量逆转录聚合酶链反应（qRT-PCR）评估了 30 例低级别、非浸润性（pTa）和 30 例高级别、浸润性（pT2-3）尿路上皮癌患者手术标本中的 14 种 miRNA 的表达情况。对照组为 5 例因良性前列腺增生接受手术治疗的患者的正常膀胱组织。内参对照物为 RNU-43 和 RNU-48。比较 miRNA 图谱并构建 Kaplan-Meier 曲线以分析无复发生存和疾病特异性生存。
miR-100 在 100%的低级别 pTa 标本中表达下调（p<0.001），miR-10a 在 73.3%的标本中表达上调（p<0.001）。miR-21 和 miR-205 在高级别 pT2-3 疾病中表达上调（p=0.02 和<0.001）。其他 miRNA 的水平与正常膀胱组织相似或在每个肿瘤组中表达下调。miR-21 过表达（大于 1.08）与低级别 pTa 尿路上皮癌患者的无复发生存时间缩短相关。miR-10a 水平较高（大于 2.30）与高级别 pT2-3 尿路上皮癌患者的无复发生存和疾病特异性生存时间缩短相关。
在这两个尿路上皮癌组中，有 4 种 miRNA 表达差异。miR-100 在低级别 pTa 肿瘤中表达下调，miR-10a 表达上调。miR-21 和 miR-205 在 pT2-3 疾病中表达上调。此外，miR-10a 和 miR-21 过表达与无复发生存和疾病特异性生存时间缩短相关。miRNAs 可被纳入尿路上皮癌的分子通路。这些 miRNA 也可以作为新的诊断或预后标志物和新的靶标药物。
