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Ion mobility mass spectrometry of human melanoma gangliosides.
Biochimie ( IF 3.3 ) Pub Date : 2020-08-25 , DOI: 10.1016/j.biochi.2020.08.011
Mirela Sarbu 1 , David E Clemmer 2 , Alina D Zamfir 3
Affiliation  

Malignant melanoma is an aggressive type of skin cancer, rarely detected in the early stages. Various sets of methods and techniques, including dermatoscopical inspection of the “ABCDE” signs of the lesion, imaging techniques or microscopical, immunohistochemical and serological biomarkers are available and used nowadays to diagnose malignant melanoma. To date, different biomarkers were proposed for melanoma, but only a few, including circulating proteins, such as lactate dehydrogenase, molecular and metabolite biomarkers, have reached clinical applications. Gangliosides represent an emerging class, being used as tumor markers and targets of antibody therapy in melanomas, based on their elevated abundance in melanoma, especially of GM3 and GD3, when compared with the corresponding normal tissues. The conjunction of mass spectrometry (MS) with ion mobility separation (IMS) demonstrated an elevated potential in detection and identification of low abundant components, with biomarker role, in extremely complex biological mixtures. Therefore, here, a native ganglioside extract originating from human melanoma was investigated for the first time by IMS MS to provide the first profiling of gangliosides in this type of cancer. The present approach revealed the high incidence of species belonging to GD3 and GM3 classes, as well as of de-N-acetyl GM3 (d-GM3) and de-N-acetyl GD3 (d-GD3), characteristic for human melanoma. Additionally, the structure of two molecules characterized by shorter glycan chains associated to melanoma, were investigated in detail. The present approach brings valuable data related to this type of cancer, completing the existing inventory of melanoma-associated biomarkers and opens new directions for further research in this field.



中文翻译:

人黑素瘤神经节苷脂的离子迁移质谱。

恶性黑色素瘤是一种侵袭性皮肤癌,在早期很少发现。各种方法和技术,包括病变的“ ABCDE”征兆的皮肤镜检查,成像技术或显微,免疫组织化学和血清学生物标记物,现已可用于诊断恶性黑色素瘤。迄今为止,已经提出了用于黑色素瘤的不同生物标志物,但是只有少数,包括循环蛋白,例如乳酸脱氢酶,分子和代谢物生物标志物,已经达到临床应用。神经节苷脂代表新兴的一类,由于与相应的正常组织相比,它们在黑色素瘤(尤其是GM3和GD3)中黑色素瘤的丰度升高,因此被用作黑色素瘤的肿瘤标志物和抗体治疗的靶标。质谱(MS)与离子迁移分离(IMS)的结合展示了在极其复杂的生物混合物中检测和鉴定具有生物标志物作用的低丰度组分的潜力。因此,在这里,IMS MS首次研究了源自人黑素瘤的天然神经节苷脂提取物,以提供该类型癌症中神经节苷脂的第一个概况。目前的方法表明,属于GD3和GM3类的物种以及除 IMS MS首次对源自人黑素瘤的天然神经节苷脂提取物进行了研究,以提供该类型癌症中神经节苷脂的第一个概况。目前的方法表明,属于GD3和GM3类的物种以及除 IMS MS首次对源自人黑素瘤的天然神经节苷脂提取物进行了研究,以提供该类型癌症中神经节苷脂的第一个概况。目前的方法表明,属于GD3和GM3类的物种以及除N-乙酰基GM3(d-GM3)和de- N-乙酰基GD3(d-GD3),是人类黑色素瘤的特征。另外,详细研究了以与黑色素瘤相关的较短聚糖链为特征的两个分子的结构。本方法带来了与这种类型的癌症有关的有价值的数据,完成了与黑素瘤相关的生物标记物的现有清单,并为该领域的进一步研究开辟了新的方向。

更新日期:2020-08-25
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