Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei, Taiwan.
Br J Haematol. 2021 Feb;192(3):589-598. doi: 10.1111/bjh.17231. Epub 2020 Nov 29.
Long non-coding RNAs (lncRNAs) have important functions in cancer biology. Among them, lncRNA KIAA0125 is one of the genes proposed to play a critical role in leukaemia stem cell (LSC). In this study, we aimed to investigate the clinical relevance of the expression levels of lncRNA KIAA0125 in myelodysplastic syndromes (MDS), a disease with highly heterogeneous clinical and biological features. Using RNA arrays, we measured the expression of KIAA0125 in 176 primary MDS patients. We found that higher KIAA0125 expression was associated with higher risk MDS, based on the revised International Prognostic Scoring System (IPSS-R), mutations in ASXL1 and NRAS, and predicted poorer overall survival (OS) and leukaemia-free survival (LFS). Multivariate analysis revealed that higher KIAA0125 expression was an independent, unfavourable prognostic factor for OS and LFS, irrespective of IPSS-R and mutation status. Further global gene expression profile analysis suggested a close association of higher KIAA0125 expressions with LSC signatures. The expression of KIAA0125 may be a potential biomarker to guide the treatment choice in MDS patients, especially those with lower risk subtypes, in whom palliative treatment is usually used.
长链非编码 RNA(lncRNA)在癌症生物学中具有重要功能。其中,lncRNA KIAA0125 是被提议在白血病干细胞(LSC)中发挥关键作用的基因之一。在这项研究中,我们旨在研究 lncRNA KIAA0125 在骨髓增生异常综合征(MDS)中的表达水平与临床的相关性,该疾病具有高度异质性的临床和生物学特征。我们使用 RNA 微阵列测量了 176 例原发性 MDS 患者中 KIAA0125 的表达。我们发现,根据修订后的国际预后评分系统(IPSS-R)、ASXL1 和 NRAS 突变以及预测的总生存期(OS)和无白血病生存期(LFS)较差,较高的 KIAA0125 表达与更高风险 MDS 相关。多变量分析表明,无论 IPSs-R 和突变状态如何,较高的 KIAA0125 表达都是 OS 和 LFS 的独立不良预后因素。进一步的全基因表达谱分析表明,较高的 KIAA0125 表达与 LSC 特征密切相关。KIAA0125 的表达可能是 MDS 患者治疗选择的潜在生物标志物,特别是那些低风险亚型的患者,通常使用姑息治疗。