Cancer Biomark. 2018;23(4):485-494. doi: 10.3233/CBM-181405.
This study aimed to explore the correlation of long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) expression with clinicopathological features and its predictive value for treatment response and survival profiles in refractory or relapsed acute myeloid leukemia (R/R AML) patients.
Seventy three R/R AML patients who received cladribine combined with cytarabine and granulocyte colony-stimulating factor (G-CSF) (CLAG) or fludarabine combined with cytarabine and G-CSF (FLAG) based chemotherapy and 37 non-malignant controls were recruited. LncRNA TUG1 expression was detected in bone marrow sample obtained before treatment. Complete response (CR), partial response (PR), overall response rate (ORR) and overall survival (OS) were evaluated.
LncRNA TUG1 expression was upregulated in R/R AML patients compared to controls. It was also elevated in R/R AML patients with age ⩾ 60 years (vs. age < 60 years, P= 0.030) and in patients with secondary AML (vs. primary AML, P= 0.035). R/R AML patients with lncRNA TUG1 high expression achieved numerically lower CR (P= 0.053), decreased ORR (P= 0.028) and shorter OS (P< 0.001) than patients with lncRNA TUG1 low expression. Univariate logistic regression and COX's regression disclosed that lncRNA TUG1 high expression correlated with declined ORR, numerically decreased CR, and reduced OS. Furthermore, multivariate analyses verified that lncRNA TUG1 high expression was an independent predictive factor for decreased ORR and worse OS.
In conclusion, lncRNA TUG1 expression was elevated in R/R AML patients, and it might serve as a potential biomarker for poor prognosis in R/R AML patients treated with CLAG or FLAG based chemotherapy.
本研究旨在探讨长链非编码 RNA 牛磺酸上调基因 1(lncRNA TUG1)表达与临床病理特征的相关性,及其对难治性或复发性急性髓系白血病(R/R AML)患者治疗反应和生存谱的预测价值。
纳入 73 例接受克拉屈滨联合阿糖胞苷和粒细胞集落刺激因子(G-CSF)(CLAG)或氟达拉滨联合阿糖胞苷和 G-CSF(FLAG)化疗的 R/R AML 患者和 37 例非恶性对照者。在治疗前采集骨髓样本检测 lncRNA TUG1 表达。评估完全缓解(CR)、部分缓解(PR)、总缓解率(ORR)和总生存期(OS)。
与对照组相比,R/R AML 患者的 lncRNA TUG1 表达上调。在年龄 ⩾ 60 岁的 R/R AML 患者(vs. 年龄 < 60 岁,P= 0.030)和继发性 AML 患者(vs. 原发性 AML,P= 0.035)中,lncRNA TUG1 的表达也升高。lncRNA TUG1 高表达的 R/R AML 患者获得 CR 的比例较低(P= 0.053),ORR 降低(P= 0.028),OS 缩短(P< 0.001),lncRNA TUG1 低表达的 R/R AML 患者。单因素 logistic 回归和 COX 回归显示,lncRNA TUG1 高表达与 ORR 下降、CR 降低、OS 缩短相关。此外,多因素分析证实 lncRNA TUG1 高表达是 ORR 降低和 OS 降低的独立预测因子。
总之,lncRNA TUG1 在 R/R AML 患者中表达上调,可能作为 CLAG 或 FLAG 为基础化疗治疗的 R/R AML 患者不良预后的潜在生物标志物。