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IUBMB Life. 2016 Oct;68(10):817-22. doi: 10.1002/iub.1557. Epub 2016 Sep 18.

Identification of arginine and its "Downstream" molecules as potential markers of breast cancer.

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Cancer center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People's Republic of China.
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China.
Runsheng Kangtai Biomedical Technology Co.Ltd, Jinzhou, People's Republic of China.
Cancer center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People's Republic of China.


Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide. Arginine is a semiessential amino acid in humans and is essential for several biological pathways in malignant and normal cells, such as ornithine and N1, N12-diacetylspermine (DiAcSpm). This study aimed to determine the role of arginine and these downstream molecules in BC. Plasma arginine, ornithine, and arginine-to-ornithine ratio (AOR) were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urine samples were measured by the colloid gold aggregation to test determination of urinary diAcSpm. A principal component analysis was performed to evaluate the results observed between breast tumor and control characteristics. Differences in individual metabolite concentrations between BC patients and controls were tested by receiver operating characteristics (ROC) analyses. Student's t tests were used to detect the differences between two groups of normally distributed variables, and Wilcoxon sign rank tests were performed for asymmetrically distributed variables. As we analyzed, BC patients had lower plasma arginine and arginine/ornithine level, and higher plasma ornithine and urinary DiAcSpm concentrations as compared with control patients (P = 0.028, 0.020, 0.002, and 0.011, respectively). And the ROC curve was drawn and the area under the curve of the metabolites was calculated to be 0.659 (P = 0.028), 0.645 (P = 0.045), 0.7233 (P = 0.002), 0.683 (P = 0.011), respectively. In addition, our analysis showed that arginine concentrations and AOR had a positive correlation with ER status, while ornithine had a negative correlation with T stage (P = 0.042, 0.023, respectively).In conclusion, arginine and these downstream molecules were biomarkers for BC. More studies are needed to highlight the theoretical strengths.


DiAcSpm; arginine; biomarker; breast cancer; ornithine

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