MicroRNA-182在判断淋巴细胞肿瘤患者糖皮质激素耐药中的应用

Application of miR-182 for Determination of Glucocorticoid-Resistant Patients with Lymphoid Malignancy

目的:研究淋巴细胞肿瘤患者miR-182表达与糖皮质激素耐药的相关性及其诊断价值。方法:运用RTPCR方法检测淋巴瘤患者(68例,骨髓标本20例,血浆标本48例),多发性骨髓瘤患者(24例,骨髓标本14例,血浆标本10例),急性淋巴细胞白血病患者(3例,血浆3例),非淋巴系统疾病患者(18例,骨髓8例,血浆10例)miR-182的表达。结果:难治的淋巴细胞肿瘤患者的miR-182的表达量明显高于初治患者(P<0.05)。初治淋巴细胞肿瘤患者的miR-182的表达量同正常对照组之间无显著差异。患者的miR-182的表达,随糖皮质激素用量增加而增高(P<0.01)。当骨髓淋巴细胞miR-182表达为10.09,诊断淋巴肿瘤细胞糖皮质激素耐药的灵敏度为100%,特异度为88.2%;血浆miR-182为1.393,诊断淋巴肿瘤细胞糖皮质耐药的灵敏度为90.9%,特异度为51.3%。结论:发生糖皮质激素耐药的淋巴细胞肿瘤的miR-182表达明显上调。miR-182作为一种新的生物标志物可以应用于淋巴细胞肿瘤糖皮质激素耐药的诊断。

Objective： To validate the clinical relationship between miR-182 and glucocorticoid-resistance in patients with lymphoid malignancy. Methods： Real-time quantitative PCR（qRT-PCR） was employed to detect the expression of miR-182 in lymphoma patients （68 cases, the specimens indluded bone marrow of 20 cases, and plasma of 48 cases）, multiple myeloma patients （24 cases, the specimens included bone marrow of 14 cases and plasma of 10 cases）, ALL patients （3 cases, specimen was plasma of 3 cases） and non-lymphotic system disorder patients （18 cases, specimens included bone marrow of 8 cases and plasma of 10 cases）. Results： The expression of miR-182 in refractory lymphoblastic tumor patients was significantly higher than that in initial treatment group （P 〈 0.05 ） ; the expression of miR-182 in initial treatment patients was not significantly different from the controls. The expression level of miR-182 in plasma of lymphoid malignancy patient significantly correlated with their used dosage of corticosteroids （ P 〈 0.05 ）. When the expression level of miR-182 in bone marrow cells was 10.09, its sensitivity and specificity for diagnosis were 100% and 88.2% respectively; when the expression level of miR-182 in plasma was 1. 393, its sensitivity and specificity for diagnosis of glucocorticoid resistance of lymphoblastic tmnor cells were 90.9% and 51.3% respectively. Conclusion：The expression of miR-182 in lymphoblastic tumor with glucocorticoid resistance is significantly up- regulated, suggesting that the glucocorticoid resistance of lymphoblastic tumor is related with the over-expression of miR- 182. The miR-182 is expected as a new biomarker for the diagnosis of glucocorticoid resistant lymphoblastic tumor.