Translational Cancer Research Group, Institute of Medical Biology, UiT The Arctic University of Norway, 9037, Tromsø, Norway.
Department of Clinical Pathology, University Hospital of North Norway, 9038, Tromsø, Norway.
Sci Rep. 2019 Jan 23;9(1):386. doi: 10.1038/s41598-018-36854-7.
A large number of miRNAs influence key cellular processes involved in prostate tumorigenesis. Previous studies have demonstrated high expression of miRNAs in human prostate cancer (PC) tissues and cell lines. In previous microarray data, we found miR-141 to be upregulated and miR-145 to be downregulated in PC. In this large PC cohort (n = 535), we explored the prognostic role of miR-141 and miR-145 in PC. Tumor epithelial (TE) and tumor stromal (TS) areas were evaluated separately and combined (TE + TS). In situ hybridization was used to evaluate the expression of the miRNAs. We found that miR-141 (TE) correlated significantly to Gleason score ≥8 (p = 0.040) and large tumor size (≥20 mm, p = 0.025) and miR-141 (TE + TS) to Gleason grade (p = 0.001). MiR-145 correlated to pT-stage (p = 0.038), tumor size (p = 0.025), Gleason grade (p = 0.051) and PSA (p = 0.032). In univariate analysis miR-141 (TE + TS) was significantly associated with biochemical failure-free survival (BFFS, p = 0.007) and clinical failure-free survival (CFFS, p = 0.021). For miR-145, there were no differences between patients with high versus low expression. In multivariate analysis overexpression of miR-141 in tumor epithelium and tumor stroma was significantly associated with BFFS (HR = 1.07 CI95% 1.00-1.14, p = 0.007). To conclude, high expression of miR-141 appears associated with increased risk of biochemical PC recurrence.
大量 miRNA 影响涉及前列腺肿瘤发生的关键细胞过程。先前的研究表明,miRNA 在人类前列腺癌(PC)组织和细胞系中高表达。在之前的微阵列数据中,我们发现 miR-141 在 PC 中上调,miR-145 下调。在这个大型 PC 队列(n=535)中,我们探讨了 miR-141 和 miR-145 在 PC 中的预后作用。分别评估肿瘤上皮(TE)和肿瘤基质(TS)区域,并将其合并(TE+TS)。使用原位杂交评估 miRNA 的表达。我们发现 miR-141(TE)与 Gleason 评分≥8(p=0.040)和大肿瘤大小(≥20mm,p=0.025)显著相关,miR-141(TE+TS)与 Gleason 分级相关(p=0.001)。miR-145 与 pT 分期(p=0.038)、肿瘤大小(p=0.025)、Gleason 分级(p=0.051)和 PSA(p=0.032)相关。单因素分析显示,miR-141(TE+TS)与生化无复发生存(BFFS,p=0.007)和临床无复发生存(CFFS,p=0.021)显著相关。对于 miR-145,高表达和低表达的患者之间没有差异。多因素分析显示,肿瘤上皮和肿瘤基质中 miR-141 的高表达与 BFFS 显著相关(HR=1.07,95%CI95%1.00-1.14,p=0.007)。总之,miR-141 的高表达似乎与生化 PC 复发风险增加相关。