Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
Biomed Pharmacother. 2020 Mar;123:109750. doi: 10.1016/j.biopha.2019.109750. Epub 2019 Dec 28.
Although the management of patients with renal cell carcinoma (RCC) has changed drastically in recent years, it is still faced with the evolving challenge. Elucidation of the mechanisms underlying RCC will help the development of therapies, as well as biomarkers for early diagnosis. In this study, ccRCC tissues from patients in different stages were subject to iTRAQ-based proteomics analysis. 130 common differentially expressed proteins (DEPs) in different stages were found and lipid metabolism pathway was obviously dysregulated in all stages. These 130 common DEPs were enriched in four highly connected subnetworks including metabolic pathway, the TCA cycle, oxidative phosphorylation and fatty acid metabolism. ECHS1, a key enzyme in fatty acid metabolism, was further investigated. ECHS1 expression was significantly downregulated in ccRCC tissues and ECHS1 level discriminated ccRCC tissues in general and in stage I from adjacent normal tissues well and with the area under the receiver operating characteristic curve (AUC) of more than 0.7. ECHS1 overexpression suppressed RCC cell proliferation and migration through inhibiting mTOR pathway activation. ECHS1 may be a novel target for ccRCC therapeutic interventions and diagnostic biomarker for ccRCC.
尽管近年来肾细胞癌 (RCC) 患者的治疗管理发生了重大变化，但仍面临着不断发展的挑战。阐明 RCC 的发病机制将有助于开发治疗方法和早期诊断的生物标志物。在这项研究中，对不同阶段的 ccRCC 组织进行了基于 iTRAQ 的蛋白质组学分析。发现了 130 个在不同阶段共同差异表达的蛋白质（DEPs），并且所有阶段的脂质代谢途径都明显失调。这 130 个共同的 DEPs 富集在四个高度连接的子网络中，包括代谢途径、三羧酸循环、氧化磷酸化和脂肪酸代谢。脂肪酸代谢中的关键酶 ECHS1 进一步被研究。ECHS1 在 ccRCC 组织中的表达显著下调，ECHS1 水平可以很好地区分 ccRCC 组织和 I 期 ccRCC 组织与相邻正常组织，并且其曲线下面积（AUC）大于 0.7。ECHS1 过表达通过抑制 mTOR 通路的激活抑制 RCC 细胞的增殖和迁移。ECHS1 可能是 ccRCC 治疗干预的新靶点和 ccRCC 的诊断生物标志物。
