[Clinical significance of S100A6 and Notch1 in multiple myeloma patients]

Zhonghua Xue Ye Xue Za Zhi. 2017 Apr 14;38(4):285-289. doi: 10.3760/cma.j.issn.0253-2727.2017.04.005.
[Article in Chinese]

Abstract

Objective: To investigate the expression levels of S100A6, Notch1 in multiple myeloma (MM) patients and its clinical significance. Mathods: The expression levels of S100A6, Notch1 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 Notch1 in bone marrow biopsy samples and intramedullary metastases soft tissues. RQ-PCR and Western blot were used to test the changes of Notch1 mRNA and Notch1 protein in U266 MM cells after S100A6 silenced by siRNA. Results: ①The expression levels of S100A6, Notch1 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 Notch1 (5.71±3.96) , as compared to those without extra medullary metastases. ②S100A6 expression was positive correlation with Notch1 (r=0.505, P=0.007) . ③S100A6 and Notch1 proteins were positive in plasma cells of bone marrow biopsy samples and intramedullary metastases soft tissues. ④The Notch1 mRNA and Notch1 expression decreased significantly after 48 hours treatment by S100A6 siRNA in U266 cells. Conclusion: S100A6 and Notch1 were closely associated with MM progress and intramedullary metastasis. They have significant correlation and might be as two prognostic molecular markers in MM.

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。.

Keywords: Calgranulin A; Multiple myeloma; Receptor, Notch1.

MeSH terms

  • Bone Marrow
  • Cell Cycle Proteins
  • Humans
  • Multiple Myeloma*
  • Plasma Cells
  • RNA, Messenger
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Receptor, Notch1
  • S100 Calcium Binding Protein A6

Substances

  • Cell Cycle Proteins
  • NOTCH1 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptor, Notch1
  • S100 Calcium Binding Protein A6
  • S100A6 protein, human

Grants and funding

基金项目:南京医科大学科技发展基金重点项目(2012NJMU089);江苏省“六大人才高峰”第11批次高层人才选拔培养资助项目(WSN-019)