Yu Zhihao, Huang Ming, Clowers Brian H
Department of Chemistry, Washington State University, Pullman, WA, United States.
Environmental Toxicology Graduate Program, University of California, Riverside, CA, United States.
Clin Mass Spectrom. 2018 Aug 3;10:16-24. doi: 10.1016/j.clinms.2018.08.001. eCollection 2018 Dec.
Melanoma accounts for more than 60% of deaths associated with skin cancer, making its early detection through dermatological screening essential for improved treatment outcomes. Early detection and successful treatment of melanoma can dramatically increase the 5-year survival rate from 14 to 98%. To support such efforts, comprehensive identification of metabolite patterns capable of describing cancer progression will help support the foundational knowledge necessary to build early detection platforms for intervention prior to metastasis. Using an UPLC-MS, as part of a cell-based, untargeted metabolomics approach, we profiled the metabolomes of WM-226-4 and WM-115 cells. Derived from the metastatic and the primary sites of the same individual, these two cell lines represent a paired melanoma cancer cell line. Progenesis and MetaboAnalyst, platforms dedicated to metabolomics data analysis, were used to establish a panel of differentially expressed metabolites across these two stages of melanoma. In addition, was used to identify the affected pathways. A total of 12 differentially expressed metabolites including amino acids, carnitine, acylcarnitine, and a limited set of lipids were identified. The significantly differing metabolites are components of a diverse set of metabolic pathways (e.g., glycerophospholipid metabolism, carnitine shuttle, tryptophan metabolism), that have biological implications for the survival and dissemination of metastatic melanoma cells.
黑色素瘤占皮肤癌相关死亡人数的60%以上，因此通过皮肤科筛查进行早期检测对于改善治疗结果至关重要。黑色素瘤的早期检测和成功治疗可将5年生存率从14%显著提高到98%。为支持此类工作，全面识别能够描述癌症进展的代谢物模式将有助于为建立转移前干预的早期检测平台提供必要的基础知识。作为基于细胞的非靶向代谢组学方法的一部分，我们使用超高效液相色谱-质谱联用仪（UPLC-MS）对WM-226-4和WM-115细胞的代谢组进行了分析。这两种细胞系源自同一个体的转移部位和原发部位，代表了一对配对的黑色素瘤癌细胞系。使用专门用于代谢组学数据分析的Progenesis和MetaboAnalyst平台，在黑色素瘤的这两个阶段建立了一组差异表达的代谢物。此外，还用于识别受影响的途径。共鉴定出12种差异表达的代谢物，包括氨基酸、肉碱、酰基肉碱和一组有限的脂质。这些显著不同的代谢物是多种代谢途径（如甘油磷脂代谢、肉碱穿梭、色氨酸代谢）的组成部分，对转移性黑色素瘤细胞的存活和扩散具有生物学意义。
