Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200092, P.R. China.
Mol Med Rep. 2018 Aug;18(2):1473-1484. doi: 10.3892/mmr.2018.9139. Epub 2018 Jun 6.
Long non-coding RNAs (lncRNAs) are transcripts characterized by >200 nucleotides, without validated protein production. Previous studies have demonstrated that certain lncRNAs have a critical role in the initiation and development of acute myeloid leukemia (AML). In the present study, the subtype‑specific lncRNAs in AML was identified. Following the exclusion of the subtype‑specific lncRNAs, the prognostic value of lncRNAs was investigated and a three‑lncRNA expression‑based risk score [long intergenic non‑protein coding RNA 926, family with sequence similarity 30 member A and LRRC75A antisense RNA 1 (LRRC75A‑AS1)] was developed for AML patient prognosis prediction by analyzing the RNA‑seq data of AML patients from Therapeutically Available Research to Generate Effective Treatments (TARGET) and The Cancer Genome Atlas (TCGA) projects. In the training set obtained from TARGET, patients were divided into poor and favorable prognosis groups by the median risk score. The prognostic effectiveness of this lncRNA risk score was confirmed in the validation set obtained from TCGA by the same cut‑off. Furthermore, the lncRNA risk score was identified as an independent prognostic factor in the multivariate analysis. As further verification of the independent prognostic power of the lncRNA risk score, stratified analysis was performed by a cytogenetics risk group and revealed a consistent result. The prognostic predictive ability of the risk score was compared with the cytogenetics risk group by time‑dependent receiver operating characteristic curves analysis. It was revealed that the combination of the lncRNA risk score and cytogenetics risk group provided a higher prognostic value than a single prognostic factor. The present study also performed co‑expression analysis to predict the potential regulatory mechanisms of these lncRNAs in a cis/trans/competing endogenous RNA manner. The results suggested that LRRC75A‑AS1 was highly associated with the target genes of transcription factors tumor protein 53 and ETS variant 6. Overall, these results highlighted the use of the three‑lncRNA expression‑based risk score as a potential molecular biomarker to predict the prognosis in AML patients.
长链非编码 RNA（lncRNA）是一类长度大于 200 个核苷酸的转录本，没有经过验证的蛋白质产物。先前的研究表明，某些 lncRNA 在急性髓系白血病（AML）的发生和发展中具有关键作用。本研究鉴定了 AML 中的亚型特异性 lncRNA。在排除亚型特异性 lncRNA 后，研究了 lncRNA 的预后价值，并通过分析来自治疗性可及研究以产生有效治疗（TARGET）和癌症基因组图谱（TCGA）项目的 AML 患者的 RNA-seq 数据，开发了基于三个 lncRNA 表达的风险评分[长基因间非蛋白编码 RNA 926、家族与序列相似性 30 成员 A 和 LRRC75A 反义 RNA 1（LRRC75A-AS1）]，用于预测 AML 患者的预后。在 TARGET 获得的训练集中，通过风险评分中位数将患者分为预后不良和预后良好两组。通过相同的截止值，在 TCGA 获得的验证集中验证了该 lncRNA 风险评分的预后有效性。此外，在多变量分析中，该 lncRNA 风险评分被确定为独立的预后因素。作为对 lncRNA 风险评分独立预后能力的进一步验证，通过细胞遗传学风险组进行分层分析，得到了一致的结果。通过时间依赖性接收器操作特征曲线分析比较了风险评分的预后预测能力与细胞遗传学风险组。结果表明，lncRNA 风险评分与细胞遗传学风险组的组合提供了比单一预后因素更高的预后价值。本研究还进行了共表达分析，以预测这些 lncRNA 以顺式/反式/竞争内源性 RNA 方式的潜在调节机制。结果表明，LRRC75A-AS1 与转录因子肿瘤蛋白 53 和 ETS 变体 6 的靶基因高度相关。总之，这些结果强调了使用基于三个 lncRNA 表达的风险评分作为预测 AML 患者预后的潜在分子生物标志物。
