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靶向和非靶向代谢组学方法揭示的多发性骨髓瘤血清代谢组学改变:一项初步研究

Serum metabolomic alterations in multiple myeloma revealed by targeted and untargeted metabolomics approaches: a pilot study.

作者信息

Chanukuppa Venkatesh, More Tushar H, Taunk Khushman, Taware Ravindra, Chatterjee Tathagata, Sharma Sanjeevan, Rapole Srikanth

机构信息

Proteomics Lab, National Centre for Cell Science Ganeshkhind Pune-411007 MH India

Savitribai Phule Pune University Ganeshkhind Pune-411007 MH India.

出版信息

RSC Adv. 2019 Sep 18;9(51):29522-29532. doi: 10.1039/c9ra04458b.

Abstract

Multiple myeloma (MM) is the second most prevalent hematological malignancy characterized by rapid proliferation of plasma cells, which leads to overproduction of antibodies. MM affects around 15% of all hemato-oncology cases across the world. The present study involves identification of metabolomic alterations in the serum of an MM cohort compared to healthy controls using both LC-MRM/MS based targeted and GC-MS based untargeted approaches. Several MM specific serum metabolomic signatures were observed in this study. A total of 54 metabolites were identified as being significantly altered in MM cohort, out of which, 26 metabolites were identified from LC-MRM/MS based targeted analysis, whereas 28 metabolites were identified from the GC-MS based untargeted analysis. Receiver operating characteristic (ROC) curve analysis demonstrated that six metabolites each from both the datasets can be projected as marker metabolites to discriminate MM subjects with higher specificity and sensitivity. Moreover, pathway analysis deciphered that several metabolic pathways were altered in MM including pyrimidine metabolism, purine metabolism, amino acid metabolism, nitrogen metabolism, sulfur metabolism, and the citrate cycle. Comprehensively, this study contributes valuable information regarding MM induced serum metabolite alterations and their pathways, which could offer further insights into this cancer.

摘要

多发性骨髓瘤(MM)是第二常见的血液系统恶性肿瘤,其特征为浆细胞快速增殖,导致抗体过度产生。MM影响全球约15%的血液肿瘤病例。本研究采用基于液相色谱-多反应监测/质谱(LC-MRM/MS)的靶向方法和基于气相色谱-质谱(GC-MS)的非靶向方法,对MM队列血清与健康对照血清中的代谢组学变化进行鉴定。本研究观察到了几种MM特异性血清代谢组学特征。总共54种代谢物在MM队列中被鉴定为有显著变化,其中,26种代谢物是通过基于LC-MRM/MS的靶向分析鉴定出来的,而28种代谢物是通过基于GC-MS的非靶向分析鉴定出来的。受试者工作特征(ROC)曲线分析表明,两个数据集中各有六种代谢物可作为标记代谢物,以更高的特异性和敏感性区分MM患者。此外,通路分析表明,MM中有几种代谢途径发生了改变,包括嘧啶代谢、嘌呤代谢、氨基酸代谢、氮代谢、硫代谢和柠檬酸循环。综合来看,本研究提供了有关MM诱导的血清代谢物变化及其途径的有价值信息,这可能为深入了解这种癌症提供进一步的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d932/9071903/8911e3f108c0/c9ra04458b-f1.jpg

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