Division of Tumor Pathology, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Prostate. 2013 Jun;73(8):827-34. doi: 10.1002/pros.22626. Epub 2012 Nov 26.
Expression profiles of some microRNAs (miRNAs) were associated with clinicopathological findings in human prostate cancer (PC), but the relative expression of miRNAs among Gleason patterns (GPs) remains unclear. In this study, we investigated the expression of several known microRNAs in each GP of PC.
Formalin-fixed, paraffin embedded (FFPE) tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n = 43, including (GP 3) n = 22, (GP 4) n = 35, and (GP 5) n = 12) and needle biopsy (patient set 2, n = 10, (GP 4) n = 10). Cancer tissues from each GP and adjacent normal counterparts were separately collected using laser-captured microdissection (LCM). Real-time RT-PCR was performed to determine the relative expression of miRNAs, including miR-31-5p, -34c-5p, -96-5p, -182-5p, -183-5p, -205-5p, -221-3p, and -222-3p, which were currently reported to be involved in PC progression.
In radical prostatectomy samples, relative expression of miR-31-5p, miR-34c-5p, and miR-205-5p in any GP was significantly decreased compared to normal counterpart. However, no significant difference was detected among GP 3, GP 4, and GP 5. Meanwhile, in the same GP4, expression of miR-31-5p miR-182-5p, and miR-205-5p in cancer tissues obtained from high grade cancer was significantly higher than those obtained from intermediate grade cancer. Validation study using biopsy samples revealed that the relative expression of miR-182-5p was statistically higher in high grade cancer even in same GP4.
We confirmed the expression of miR-182-5p depended on the cancer grade even in same GP 4. Expression of miRNA associated with Gleason grading system may contribute to more accurate preoperative cancer risk evaluation.
一些 microRNAs(miRNAs)的表达谱与人类前列腺癌(PC)的临床病理发现相关,但 Gleason 模式(GP)之间 miRNAs 的相对表达仍不清楚。在这项研究中,我们研究了 PC 中每个 GP 中几种已知 microRNAs 的表达。
从根治性前列腺切除术(RP)(患者集 1,n=43,包括(GP 3)n=22、(GP 4)n=35 和(GP 5)n=12)和针活检(患者集 2,n=10,(GP 4)n=10)中获得福尔马林固定、石蜡包埋(FFPE)组织样本。使用激光捕获显微切割(LCM)分别收集来自每个 GP 的癌症组织和相邻正常组织。进行实时 RT-PCR 以确定 microRNAs 的相对表达,包括 miR-31-5p、-34c-5p、-96-5p、-182-5p、-183-5p、-205-5p、-221-3p 和 -222-3p,目前报道它们参与 PC 进展。
在根治性前列腺切除术中,与正常对照相比,任何 GP 中 miR-31-5p、miR-34c-5p 和 miR-205-5p 的相对表达均显著降低。然而,GP 3、GP 4 和 GP 5 之间没有发现显著差异。同时,在同一 GP4 中,高级别癌症组织中 miR-31-5p、miR-182-5p 和 miR-205-5p 的表达明显高于中级别癌症组织。使用活检样本进行的验证研究表明,即使在同一 GP4 中,miR-182-5p 的相对表达在高级别癌症中也具有统计学意义。
我们证实了 miR-182-5p 的表达甚至在同一 GP 4 中也取决于癌症的分级。与 Gleason 分级系统相关的 miRNA 的表达可能有助于更准确的术前癌症风险评估。