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基于 LC-HRMS 和 PLS-DA 的人肾透明细胞癌组织和尿液代谢组学研究。

Metabolomic study of human tissue and urine in clear cell renal carcinoma by LC-HRMS and PLS-DA.

机构信息

Faculty of Chemistry, Rzeszow University of Technology, 35-959, Rzeszow, Poland.

Department of Microbiology and Plant Biology, University of Oklahoma, Norman, OK, 73019, USA.

出版信息

Anal Bioanal Chem. 2018 Jun;410(16):3859-3869. doi: 10.1007/s00216-018-1059-x. Epub 2018 Apr 16.

DOI:10.1007/s00216-018-1059-x
PMID:29658093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5956006/
Abstract

Renal cell carcinoma (RCC) is the most prevalent and lethal malignancy of the kidney. Despite all the efforts made, no tissue biomarker is currently used in the clinical management of patients with kidney cancer. A search for possible biomarkers in urine for clear cell renal cell carcinoma (ccRCC) has been conducted. Non-targeted metabolomic analyses were performed on paired samples of surgically removed renal cancer and normal tissue, as well as on urine samples. Extracts were analyzed by liquid chromatography/high-resolution mass spectrometry (LC-HRMS). Hydroxybutyrylcarnitine, decanoylcarnitine, propanoylcarnitine, carnitine, dodecanoylcarnitine, and norepinephrine sulfate were found in much higher concentrations in both cancer tissues (compared with the paired normal tissue) and in urine of cancer patients (compared with control urine). In contrast, riboflavin and acetylaspartylglutamate (NAAG) were present at significantly higher concentrations both in normal kidney tissue as well as in urine samples of healthy persons. This preliminary study resulted in the identification of several compounds that may be considered potential clear cell renal carcinoma biomarkers. Graphical abstract PLS-DA plot based on LC-MS data for normal and cancer human tissue samples. The aim of this work was the identification of up- and downregulated compounds that could potentially serve as renal cancer biomarkers.

摘要

肾细胞癌(RCC)是肾脏最常见和最致命的恶性肿瘤。尽管已经做出了所有努力,但目前在肾癌患者的临床管理中没有使用组织生物标志物。已经对透明细胞肾细胞癌(ccRCC)的尿液中的可能生物标志物进行了研究。对手术切除的肾癌和正常组织以及尿液样本进行了非靶向代谢组学分析。通过液相色谱/高分辨率质谱(LC-HRMS)分析提取物。羟丁酰肉碱、癸酰肉碱、丙酰肉碱、肉碱、十二烷酰肉碱和去甲肾上腺素硫酸盐在癌组织(与配对的正常组织相比)和癌症患者的尿液(与对照尿液相比)中的浓度均明显更高。相比之下,核黄素和乙酰天门冬氨酸谷氨酸(NAAG)在正常肾脏组织以及健康人的尿液样本中均以更高的浓度存在。这项初步研究确定了几种可能被认为是潜在透明细胞肾细胞癌生物标志物的化合物。基于 LC-MS 数据的正常和癌症人类组织样本的 PLS-DA 图。本工作的目的是鉴定可能作为肾癌生物标志物的上调和下调化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/9889fd26d039/216_2018_1059_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/7a6e7b5bbf26/216_2018_1059_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/3512186d51e7/216_2018_1059_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/e897aa81daff/216_2018_1059_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/9889fd26d039/216_2018_1059_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/7a6e7b5bbf26/216_2018_1059_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/3512186d51e7/216_2018_1059_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/e897aa81daff/216_2018_1059_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4847/5956006/9889fd26d039/216_2018_1059_Fig3_HTML.jpg

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