Shen Xianjuan, Ye Yan, Qi Jing, Shi Wei, Wu Xinhua, Ni Hongbing, Cong Hui, Ju Shaoqing
Surgical Comprehensive Laboratory, Affiliated Hospital of Nantong University, Nantong, P.R.
Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, P.R.
Clin Chem Lab Med. 2017 May 1;55(5):748-754. doi: 10.1515/cclm-2015-1108.
miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer.
We examined the miRNAs perturbed in CD138+ primary multiple myeloma (MM) cells, using microarray analysis and real-time quantitative PCR (RT-qPCR). Serum miR-4449 expression levels were detected from 71 primary MM patients and 46 healthy controls by RT-qPCR.
Our analysis revealed up-regulation of 54 and down-regulation of 28 miRNAs in MM subjects compared to healthy controls. miR-4449 has not been reported in MM. It was found that the relative expression of bone marrow miR-4449 in MM patients (2.14±1.42) was higher than that in healthy controls (0.815±0.165) (U=8, p=0.0093). The relative expression of serum miR-4449 in MM patients (2.11±2.10) was significantly higher than that in healthy controls (0.357±0.235) (U=374, p<0.0001) and was significantly correlated with β2M, λ light and κ light chain concentration (r=0.480, p=0.0003; r=0.560, p<0.0001; r=0.560, p<0.0001), but not correlated with the lactate dehydrogenase (LDH) concentration (r=0.247, p=0.0611). The area under the curve (AUC) of the receiver-operating characteristics (ROC) curve of serum miR-4449 was 0.885 (95% CI, 0.826-0.945), which is higher than for other markers. Combining miR-4449, λ light chain, and β2M together, the sensitivity was highest compared with λ light chain or β2M alone, or combined.
The expression levels of serum miR-4449 in MM patients were significantly higher than in healthy controls, suggesting that it may prove to be useful in the auxiliary diagnosis of MM.
微小RNA（miRNA）参与多种生物学过程，包括发育、细胞生长、细胞凋亡和造血作用，提示其在癌症中发挥作用。
我们运用微阵列分析和实时定量聚合酶链反应（RT-qPCR）检测CD138+原发性多发性骨髓瘤（MM）细胞中受干扰的miRNA。采用RT-qPCR检测71例原发性MM患者和46例健康对照者血清中miR-4449的表达水平。
我们的分析显示，与健康对照相比，MM患者中有54种miRNA上调，28种miRNA下调。MM中尚未报道miR-4449。研究发现，MM患者骨髓中miR-4449的相对表达量（2.14±1.42）高于健康对照者（0.815±0.165）（U=8，p=0.0093）。MM患者血清中miR-4449的相对表达量（2.11±2.10）显著高于健康对照者（0.357±0.235）（U=374，p<0.0001），且与β2微球蛋白、λ轻链和κ轻链浓度显著相关（r=0.480，p=0.0003；r=0.560，p<0.0001；r=0.560，p<0.0001），但与乳酸脱氢酶（LDH）浓度无关（r=0.247，p=0.0611）。血清miR-4449的受试者工作特征（ROC）曲线下面积（AUC）为0.885（95%CI，0.826-0.945），高于其他标志物。将miR-4449、λ轻链和β2微球蛋白联合起来，与单独或联合使用λ轻链或β2微球蛋白相比，敏感性最高。
MM患者血清中miR-4449的表达水平显著高于健康对照者，提示其可能在MM的辅助诊断中具有应用价值。
