Ahmed Naseer, Kidane Biniam, Wang Le, Nugent Zoann, Moldovan Nataliya, McElrea April, Shariati-Ievari Shiva, Qing Gefei, Tan Lawrence, Buduhan Gordon, Srinathan Sadeesh K, Aliani Michel
Research Institute in Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada.
Department of Radiology, Section of Radiation Oncology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Cancers (Basel). 2021 Jun 16;13(12):3012. doi: 10.3390/cancers13123012.
Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non-small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery ( < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites ( < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites ( < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.
恶性细胞中的代谢改变在肿瘤的起始、增殖和转移中起着至关重要的作用。非小细胞肺癌（NSCLC）患者的生物流体中含有具有潜在临床应用价值的代谢生物标志物。在本研究中，我们使用质谱和核磁共振波谱技术评估了早期NSCLC患者手术切除前后生物流体代谢谱的变化。35名患者的单一队列分别在手术前和手术后提供了总共29对尿液样本和32对血清样本。我们鉴定出48种代谢物的谱在手术前后有显著差异：尿液中有17种，血清中有31种。手术后上调的代谢物比例高于下调的代谢物比例（<0.01）；然而，下调代谢物的中位倍数变化（FC）高于上调代谢物（<0.05）。嘌呤/嘧啶和蛋白质的失调比其他类别的代谢物更大（每类<0.05）。一些失调的代谢物此前已与癌症相关，包括亮氨酰脯氨酸、不对称二甲基精氨酸、异戊烯基腺嘌呤、富马酸（均在手术后下调），以及N6-甲基腺苷和几种脱氧胆酸部分，它们在手术后上调。本研究确立了生物流体的代谢组学分析作为NSCLC无创诊断、筛查和监测的途径。
