Identification of arginine and its “Downstream” molecules as potential markers of breast cancer

Abstract

SummaryBreast 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 5 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 5 0.028), 0.645 (P 5 0.045), 0.7233 (P 5 0.002), 0.683 (P 5 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 5 0.042, 0.083, 0.023, respectively). In conclusion, arginine and these downstream molecules were biomarkers for BC. More studies are needed to highlight the theoretical strengths. V C 2016 IUBMB Life, 68(10): [817][818][819][820][821][822] 2016

Association of plasma arginine with breast cancer molecular subtypes in women of Liaoning province

“…ER‐positive BC patients tended to have lower levels of arginine than ER‐negative BC patients. The result was diametrically opposed to the previous reports , so that more studies were needed to verify the conclusion. ER is expressed in 75% of BC overall and is the major driver in the majority of BC, with nuclear and non‐nuclear functions .…”

“…Arginine auxotrophs are cells that lack active ASS1, the enzyme catalysing the final step in arginine biosynthesis , and that have lost the ability to synthesise arginine and have to rely on external arginine sources. The decrease in plasma arginine levels has been described in BC patients in previous studies . In addition, increased levels of arginine have been observed in breast tumours tissues compared to benign breast tissues .…”

Serum levels of polyamine synthesis enzymes increase in diabetic patients with breast cancer

“…Studies showing that changes in arginine metabolism are important in a variety of diseases such as sepsis, cancer and type II diabetes also support our findings ( 27 , 28 , 29 ). In another study supporting our findings, it was suggested that arginine/ornithine ratio (AOR) decreased in breast cancer patients and this could be a marker ( 30 ). The ornithine levels in all of the study groups were increased and statistically significant ( Table 3 ).…”

“…The difference is very significant when it is based on diabetes. Although an increase in the levels of polyamines in cancer appears to be a natural result ( 30 , 33 , 34 ), an increase in the levels of enzymes responsible for polyamine synthase pathway in breast cancer developing in the presence of diabetes is a significant finding.…”

Cerebrospinal fluid metabolomic profiles can discriminate patients with leptomeningeal carcinomatosis from patients at high risk for leptomeningeal metastasis

“…N1, N12-diacetylspermine is an amine metabolic compound known to be a urine tumor biomarker. Increased urine concentrations of N1, N12-diacetylspermine occurs in many types of cancers (e.g., breast cancer [ 17 , 18 ], colorectal cancer [ 18 ], non-small cell lung cancer [ 19 ], bladder cancer [ 20 ], metastatic and primary brain tumors including grade 3 and 4 gliomas and primary CNS lymphoma [ 21 ], hepatocellular carcinoma [ 22 ], and leukemia [ 23 ]). To the best of our knowledge, our results are the first to suggest that the CSF concentrations of N1, N12-diacetylspermine might be useful for selecting patients with cancers or brain tumors.…”