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循环 microRNA-203 在血清中作为多发性骨髓瘤新型潜在诊断标志物的临床意义。

Clinical significance of circulatory microRNA-203 in serum as novel potential diagnostic marker for multiple myeloma.

机构信息

Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.

Department of Hematology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

出版信息

J Cancer Res Clin Oncol. 2019 Jun;145(6):1601-1611. doi: 10.1007/s00432-019-02896-1. Epub 2019 Mar 19.

Abstract

PURPOSE

Multiple myeloma (MM) is a hematological malignancy marked by uncontrolled proliferation and accumulation of plasma cells in bone marrow. Despite presence of numerous diagnostic markers for MM, their invasive and non-specific nature demands identification of some effective biomarker. Small non-coding RNAs, i.e., microRNAs being secreted out in circulation could depict the change in homeostasis. Earlier, we reported diagnostic potential of a proteoglycan, Versican (VCAN) in MM, hence, VCAN linked cell-free microRNAs have been explored to study their diagnostic involvement in MM.

METHODS

Biopsy proven MM patients and controls were recruited. The relative microRNA expression of VCAN linked microRNAs (miR-143, miR-144, miR-199, and miR-203) along with levels of VCAN have been investigated in bone marrow supernatant fluid (BMSF) and blood serum and their correlation were done with clinico-pathological parameters. The diagnostic potential was assessed using ROC curve.

RESULTS

Relative microRNA expression of all microRNAs was found significantly lower in MM patients in both BMSF and serum while VCAN levels were substantially higher in patients. VCAN levels showed positive trend while microRNAs expression showed negative trend with severity of disease. miR-203 showed significant correlation with myeloma-associated parameters and also showed optimum sensitivity and specificity for diagnosis of MM in serum.

CONCLUSIONS

Downregulation of cell-free microRNAs illustrates their importance in MM. The negative trend of microRNAs with disease progression suggests their diagnostic significance. Correlation of miR-203 with myeloma clinical parameters along with optimum sensitivity and specificity affirms its non-invasive diagnostic potential in MM which could further be validated in larger patient cohort.

摘要

目的

多发性骨髓瘤(MM)是一种血液恶性肿瘤,其特征是骨髓中浆细胞不受控制地增殖和积累。尽管有许多 MM 的诊断标志物,但它们的侵袭性和非特异性需要确定一些有效的生物标志物。分泌到循环中的小非编码 RNA,即 microRNAs,可以描绘内稳态的变化。早期,我们报道了蛋白聚糖 Versican(VCAN)在 MM 中的诊断潜力,因此,探索了与 VCAN 相关的无细胞 microRNAs,以研究它们在 MM 中的诊断参与。

方法

招募了经活检证实的 MM 患者和对照者。研究了骨 marrow 上清液(BMSF)和血清中 VCAN 相关 microRNAs(miR-143、miR-144、miR-199 和 miR-203)的相对 microRNA 表达及其与临床病理参数的相关性。使用 ROC 曲线评估诊断潜力。

结果

在 BMSF 和血清中,所有 microRNAs 的相对 microRNA 表达在 MM 患者中均明显降低,而 VCAN 水平在患者中显著升高。VCAN 水平呈正趋势,而 microRNAs 表达呈负趋势,与疾病严重程度相关。miR-203 与骨髓瘤相关参数具有显著相关性,并且在血清中对 MM 的诊断具有最佳的敏感性和特异性。

结论

无细胞 microRNAs 的下调说明了它们在 MM 中的重要性。microRNAs 与疾病进展的负趋势表明了它们的诊断意义。miR-203 与骨髓瘤临床参数的相关性以及最佳的敏感性和特异性,证实了其在 MM 中的非侵入性诊断潜力,这可以在更大的患者队列中进一步验证。

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