Fahrmann Johannes F, Grapov Dmitry D, Wanichthanarak Kwanjeera, DeFelice Brian C, Salemi Michelle R, Rom William N, Gandara David R, Phinney Brett S, Fiehn Oliver, Pass Harvey, Miyamoto Suzanne
University of California, Davis, West Coast Metabolomics Center, Davis, California.
CDS Creative Data Solutions, Ballwin, MO.
Carcinogenesis. 2017 Mar;38(3):271-280. doi: 10.1093/carcin/bgw205. Epub 2017 Jan 3.
Lung cancer is the leading cause of cancer mortality in the United States with non-small cell lung cancer (NSCLC) adenocarcinoma being the most common histological type. Early perturbations in cellular metabolism are a hallmark of cancer, but the extent of these changes in early stage lung adenocarcinoma remains largely unknown. In the current study, an integrated metabolomics and proteomics approach was utilized to characterize the biochemical and molecular alterations between malignant and matched control tissue from 27 subjects diagnosed with early stage lung adenocarcinoma. Differential analysis identified 71 metabolites and 1102 proteins that delineated tumor from control tissue. Integrated results indicated four major metabolic changes in early stage adenocarcinoma: (1) increased glycosylation and glutaminolysis; (2) elevated Nrf2 activation; (3) increase in nicotinic and nicotinamide salvaging pathways; and (4) elevated polyamine biosynthesis linked to differential regulation of the SAM/nicotinamide methyl-donor pathway. Genomic data from publicly available databases were included to strengthen proteomic findings. Our findings provide insight into the biochemical and molecular biological reprogramming that may accompanies early stage lung tumorigenesis and highlight potential therapeutic targets.
肺癌是美国癌症死亡的主要原因，其中非小细胞肺癌（NSCLC）腺癌是最常见的组织学类型。细胞代谢的早期扰动是癌症的一个标志，但早期肺腺癌中这些变化的程度在很大程度上仍不清楚。在当前的研究中，采用了综合代谢组学和蛋白质组学方法来表征27例被诊断为早期肺腺癌的患者的恶性组织与配对对照组织之间的生化和分子改变。差异分析确定了71种代谢物和1102种蛋白质，这些代谢物和蛋白质区分了肿瘤组织与对照组织。综合结果表明早期腺癌有四个主要代谢变化：（1）糖基化和谷氨酰胺分解增加；（2）Nrf2激活升高；（3）烟碱和烟酰胺挽救途径增加；（4）与SAM/烟酰胺甲基供体途径的差异调节相关的多胺生物合成升高。纳入了来自公开可用数据库的基因组数据以加强蛋白质组学研究结果。我们的研究结果为早期肺肿瘤发生可能伴随的生化和分子生物学重编程提供了见解，并突出了潜在的治疗靶点。
