Division of Medical Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo, Japan.
Division of Molecular Pathology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo, Tokyo, Japan.
Sci Rep. 2016 Jun 30;6:28932. doi: 10.1038/srep28932.
Renal cell carcinoma (RCC) is the most common histological type of adult kidney cancer. In this study, we obtained lipidomic profiles of clear cell RCC (ccRCC), a major RCC subtype, by performing a lipidomic analysis of specimens of cancerous tissue and the surrounding normal renal cortex obtained from the same patients (N = 49). We also compared the lipidomic profiles with the lipogenic transcriptome of specimens of cancerous tissue and the surrounding normal renal cortex for an additional set of patient samples (N = 95). Overall, we detected 326 lipids, including phospholipids, sphingolipids, neutral lipids, and eicosanoids. The levels of more than 70% of the detected lipids were significantly different (P < 0.01, corrected by the false discovery rate). The cancerous tissue was distinguished by higher levels of ether-type phospholipids, cholesterol esters, and triacylglycerols, as well as by lower levels of phospholipids (except for phosphatidylcholines) and polyunsaturated fatty acids. Characteristic changes in the levels of mRNAs and metabolites suggested that the phosphatidylethanolamine (PE) synthesis pathway is suppressed in ccRCC and associated with cell proliferation. The present study represents the lipidomic profiles of ccRCC, which provides novel information about the metabolic changes in renal cancerous tissue and RCC pathophysiology.
肾细胞癌（RCC）是成人肾癌中最常见的组织学类型。在这项研究中，我们通过对来自同一患者的癌组织和周围正常肾皮质标本进行脂质组学分析，获得了透明细胞 RCC（ccRCC）的脂质组学图谱，ccRCC 是主要的 RCC 亚型之一（N=49）。我们还比较了癌组织和周围正常肾皮质标本的脂质组学图谱与脂质生成转录组，用于另一组患者样本（N=95）。总的来说，我们检测到 326 种脂质，包括磷脂、鞘脂、中性脂质和类二十烷酸。超过 70%的检测到的脂质水平有显著差异（P<0.01，经假发现率校正）。癌组织中醚型磷脂、胆固醇酯和三酰甘油水平较高，而磷脂（除磷脂酰胆碱外）和多不饱和脂肪酸水平较低。mRNA 和代谢物水平的特征变化表明，ccRCC 中磷脂酰乙醇胺（PE）合成途径受到抑制，与细胞增殖有关。本研究代表了 ccRCC 的脂质组学图谱，为肾癌组织中的代谢变化和 RCC 病理生理学提供了新的信息。
