Translational Cancer Research Group, Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Sci Rep. 2019 Jul 23;9(1):10662. doi: 10.1038/s41598-019-47234-0.
Prostate cancer (PC) is a highly heterogenous disease and one of the leading causes of mortality in developed countries. Recently, studies have shown that expression of immune checkpoint proteins are directly or indirectly repressed by microRNAs (miRs) in many types of cancers. The great advantages of using miRs based therapy is the capacity of these short transcripts to target multiple molecules for the same- or different pathways with synergistic immune inhibition effects. miR-424 has previously been described as a biomarker of poor prognosis in different types of cancers. miR-424 is also found to target both the CTLA-4/CD80- and PD-1/PD-L1 axis. In the present study, the clinical significance of miR-424-3p expression in PC tissue was evaluated. Naïve radical prostatectomy specimens from 535 patients was used for tissue microarray construction. In situ hybridization was used to evaluate the expression of miR-424-3p and immunohistochemistry was used for CTLA-4 protein detection. In univariate- and multivariate analyses, low expression of miR-424-3p was significant associated with clinical failure-free survival, (p = 0.004) and p = 0.018 (HR:0.44, CI95% 0.22-0.87). Low expression of miR-424-3p also associated strongly with aggressive phenotype of PC. This highlight the importance of miR-424-3p as potential target for therapeutic treatment in prostate cancer.
前列腺癌(PC)是一种高度异质性疾病,也是发达国家主要死亡原因之一。最近的研究表明,免疫检查点蛋白的表达在许多类型的癌症中被 microRNA(miRs)直接或间接抑制。利用基于 miR 的疗法的巨大优势在于,这些短转录物能够靶向相同或不同途径的多个分子,具有协同免疫抑制作用。miR-424 以前被描述为不同类型癌症中预后不良的生物标志物。miR-424 还被发现靶向 CTLA-4/CD80-和 PD-1/PD-L1 轴。在本研究中,评估了 miR-424-3p 在 PC 组织中的表达的临床意义。使用 535 名患者的天真根治性前列腺切除术标本构建组织微阵列。原位杂交用于评估 miR-424-3p 的表达,免疫组织化学用于检测 CTLA-4 蛋白。在单因素和多因素分析中,miR-424-3p 的低表达与临床无失败生存显著相关(p=0.004),p=0.018(HR:0.44,95%CI95% 0.22-0.87)。miR-424-3p 的低表达也与 PC 的侵袭性表型密切相关。这突显了 miR-424-3p 作为前列腺癌治疗潜在靶点的重要性。