S100A6、Notch1在多发性骨髓瘤患者中的表达及其临床意义

Clinical significance of S100A6 and Notchl in multiple myeloma patients

目的探讨S100A6、Notch1在多发性骨髓瘤（MM）患者中的表达及其临床意义。 方法以28例MM患者为研究对象，以20例白细胞、血小板略低但骨髓检查未见异常者为对照，采用real time PCR法检测骨髓单个核细胞S100A6、Notch1的表达；采用免疫组化染色法检测S100A6、Notch1蛋白在MM患者骨髓和髓外浸润组织活检病理切片中的表达；采用real time PCR法和Western blot法检测siRNA沉默骨髓瘤U266细胞S100A6基因后对Notch1 mRNA和蛋白水平的影响。并结合临床进行相关分析。 结果①S100A6、Notch1 mRNA表达水平：初发MM患者组分别为2.19±1.25、2.98±0.64，均高于对照组（0.71±0.20、0.58±0.39）和稳定期患者组（0.85±0.26、0.72±0.40）（P值均〈0.05）；伴髓外转移组（8例）分别为3.36±1.23、5.71±3.96，均高于无髓外转移组（20例）（1.40±0.25、1.16±1.00）。②S100A6与Notch1 mRNA表达呈正相关（r=0.505，P=0.007）。③MM患者骨髓和髓外浸润组织活检病理切片均可见浆细胞S100A6、Notch1阳性表达。④siRNA转染U266细胞48 h后S100A6基因表达沉默，Notch1 mRNA及蛋白水平明显下降。 结论S100A6、Notch1表达与MM疾病发生、进展、髓外转移相关，二者具有显著相关性，可作为MM诊断及预后的指标。

Objective To investigate the expression levels of S100A6, Notchl in multiple myeloma （MM） patients and its clinical significance. Mathods The expression levels of S 100A6, Notch 1 in 28 MM cases and 20 healthy controls were determined by real time quantitative PCR （RQ-PCR）, and their relationships with clinical features and outcomes were analyzed. Immunohistochemical was used to analysis the levels of S100A6 and Notchl in bone marrow biopsy samples and intramedullary metastases soft tissues. RQ-PCR and Western blot were used to test the changes ofNotchl mRNA and Notchl protein in U266 MM cells after S 100A6 silenced by siRNA. Results The expression levels of S 100A6, Notch l in primary MM patients was 2.19± 1.25, 2.98±0.64, significantly higher than those in controls （0.71 ±0.20, 0.58±0.39, P〈0.05） and patients in platform status （0.85±0.26, 0.72±0.40, P〈0.05）. 8 cases with intramedullary metastasis had significantly higher levels of S100A6 （3.36±1.23） and Notchl （5.71±3.96）, as compared to those without extra medullary metastases. S100A6 expression was positive correlation with Notchl （r=0.505, P=-0.007）. S100A6 and Notchl proteins were positive in plasma cells of bone marrow biopsy samples and intramedullary metastases soft tissues. The Notchl mRNA and Notchl expression decreased significantly after 48 hours treatment by S100A6 siRNA in U266 cells. Conclusion S 100A6 and Notch l were closely associated with MM progress and intramedullary metastasis. They have significant correlation and might be as two prognostic molecular markers in MM.