Abstract
BackgroundMetabolome analysis including amino acid profile is under investigation as an approach in cancer screening. The present study aims to analyze plasma free amino acid (PFAA) profiles in cancer patients and investigate their potential as biomarkers of malignancy.MethodsPlasma samples from 56 gastric cancer patients, 28 breast cancer patients, 33 thyroid cancer patients, and 137 age-matched healthy controls were collected in the study. PFAA levels were measured and their perioperative alterations were analyzed. Biological effects of ten cancer-related amino acids were further validated in gastric and breast cancer cells.ResultsWe found that PFAA profiles of cancer patients differed significantly from those of healthy controls. Decreased concentrations of PFAAs were associated with lymph node metastases in gastric cancer. Levels of PFAAs such as aspartate and alanine increased after tumor resection. PFAA levels correlated with clinical tumor markers in gastric cancer patients and pathological immunohistochemistry markers in breast cancer patients. Specifically, alanine, arginine, aspartate and cysteine had proliferative effects on breast cancer cells. Proliferation of gastric cancer cells was promoted by cysteine, but inhibited by alanine and glutamic acid. Furthermore, alanine treatment decreased total and stable fraction of gastric cancer cells, and alanine and glutamic acid induced apoptosis of gastric cancer cells.ConclusionsPFAA patterns in cancer patients are altered perioperatively. Tumor-related amino acids identified by dynamic study of PFAA patterns may have the potential to be developed as novel biomarkers for diagnosis and prognosis of cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0408-1) contains supplementary material, which is available to authorized users.
Highlights
Metabolome analysis including amino acid profile is under investigation as an approach in cancer screening
We investigated the variation of amino acids profiles between cancer patients and healthy controls (HCs), by examining peripheral blood metabolites from 56 gastric cancer (GC) patients, 28 breast cancer (BC) patients, 33 thyroid cancer (TC) patients, and 137 age-matched Healthy control (HC)
The present study demonstrates that dynamic observations of plasma free amino acid (PFAA) profiles in cancer patients may provide an insight into cancer metabolism and may be an alternative to detect tumors
Summary
Metabolome analysis including amino acid profile is under investigation as an approach in cancer screening. The present study aims to analyze plasma free amino acid (PFAA) profiles in cancer patients and investigate their potential as biomarkers of malignancy. Current cancer screening techniques such as endoscopy for gastric cancer (GC), mammography for breast cancer (BC), and ultrasound for thyroid cancer (TC) are important in clinical applications, they are limited by invasiveness, radiation exposure and high cost [2,3,4]. Preexisting biomarkers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (e.g., CA 15–3 and CA19-9) are frequently used to monitor tumor.
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