Dynamic monitoring of plasma amino acids and carnitine during chemotherapy of patients with alimentary canal malignancies and its clinical value

Onco Targets Ther. 2015 Aug 7:8:1989-96. doi: 10.2147/OTT.S86562. eCollection 2015.

Abstract

Objective: The aim of this study was to observe the plasma amino acid and carnitine characteristics in patients with metastatic gastrointestinal malignancies during chemotherapy and to identify markers for the early diagnosis and evaluation of adverse reactions and prognosis of the digestive tract malignant tumor patients.

Methods: Blood samples of 30 patients with metastatic gastrointestinal malignancies were collected at four time points: before chemotherapy, the first day after chemotherapy (+1 day), bone marrow depression period (+14 days), and hematopoietic recovery period (+21 days). The plasma amino acids and carnitine from those 30 patients were determined by high-performance liquid chromatography-tandem mass spectrometry method. Simultaneously, the levels of 21 amino acids were detected in 30 healthy individuals, who were considered as control. Biochemical indexes were also detected at four time points, adverse reactions were recorded during the chemotherapy process, and patients were followed up for 1 year to observe time to progression (TTP) and progression-free survival (PFS).

Results: Compared to healthy people in the control group, patients with malignancies showed significantly increased levels of plasma amino acids such as Arg, Asp, Cit, Gly, Orn, Tyr, Val, and carnitine (such as C2). The levels of compounds such as C3, Asn, Leu, Lys, Pip, Pro, C0, C5:1 decreased significantly before chemotherapy. The levels of Cit, Cys, Lys, Pro, Tyr, Val, C0, and C2 decreased significantly on the second day of chemotherapy (+1 day), whereas the level of C3 increased significantly. During myelosuppression (+14 days), the levels of Asp, Cit, Met, and Orn were observed to still decrease significantly, whereas the level of Val appeared to increase significantly. The levels of Asp, Glu, and Met were clearly different among patients with gastric carcinoma, rectal cancer, and colon cancer. Compared to the control group, aspartate amino transferase and alanine aminotransferase were found to be higher in eight patients with hypocarnitinemia, yet TTP, PFS, and RR (response rate) were lower. No significant difference was observed for adverse reactions. The indexes in 12 patients with citrullinemia showed no difference compared with control group. All the results showed statistically significant differences (P<0.05).

Conclusion: Real-time monitoring of plasma amino acids and carnitine in patients with metastatic gastrointestinal malignancies can directly reflect the body's metabolism and nutritional status. The results provide a reference for nutrition therapy or support for patients with alimentary canal malignancies. Hypocarnitinemia is a risk factor for gastrointestinal cancer patients and affects TTP, PFS, and RR by liver function. This study shows that tandem mass spectrometry can be used to detect blood amino acids and carnitine spectrum may be used for an early diagnosis and evaluation of adverse reactions and prognosis of the digestive tract malignant tumor patients.

Keywords: carnitine and acylcarnitines; chemotherapy; gastrointestinal cancer; high-performance liquid chromatography–tandem mass spectrometry; plasma amino acid.