National Institute for Research and Development in Electrochemistry and Condensed Matter, Timisoara, Romania.
Department of Chemistry, Indiana University, Bloomington, IN, USA.
Biochimie. 2020 Oct;177:226-237. doi: 10.1016/j.biochi.2020.08.011. Epub 2020 Aug 25.
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.
恶性黑色素瘤是一种侵袭性皮肤癌，早期很少被发现。目前有多种方法和技术，包括病变的“ABCDE”征象的皮肤镜检查、成像技术或显微镜下、免疫组织化学和血清生物标志物，用于诊断恶性黑色素瘤。迄今为止，已经提出了不同的黑色素瘤生物标志物，但只有少数几种，包括循环蛋白，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。神经节苷脂是一个新兴的类别，基于其在黑色素瘤中的丰度增加，特别是 GM3 和 GD3，与相应的正常组织相比，它们被用作黑色素瘤的肿瘤标志物和抗体治疗的靶点。质谱（MS）与离子淌度分离（IMS）的结合显示出在检测和鉴定极低丰度成分方面具有很高的潜力，这些成分具有生物标志物作用，存在于极其复杂的生物混合物中。因此，在这里，首次通过 IMS MS 对源自人类黑色素瘤的天然神经节苷脂提取物进行了研究，为这种癌症中的神经节苷脂提供了首次分析。本方法揭示了属于 GD3 和 GM3 类以及去 N-乙酰 GM3（d-GM3）和去 N-乙酰 GD3（d-GD3）的物种的高发率，这些物种是人类黑色素瘤的特征。此外，还详细研究了与黑色素瘤相关的两种分子的结构，这些分子具有较短的聚糖链。本方法提供了与这种癌症相关的有价值的数据，补充了现有的黑色素瘤相关生物标志物清单，并为该领域的进一步研究开辟了新的方向。
