ALTERNATIVE METHOD FOR THE DIAGNOSIS OF EARLY CANCER USING PLASMA FREE AMINO ACID PROFILES

由于代谢变化，各种疾病患者的氨基酸平衡会发生变化。众所周知，癌细胞中的新陈代谢也发生了显著的变化。因此，氨基酸图谱可能是各种癌症的有用生物标记物。本研究通过对结直肠癌患者、乳腺癌患者和健康对照组的静脉血样本进行多因素分析，发现结直肠癌患者和乳腺癌患者的血浆氨基酸谱有显著变化。采用液-质联用(LC/MS)测定血浆游离氨基酸。基于氨基酸图谱，使用多个Logistic回归模型来区分结直肠癌或乳腺癌患者和对照组。以受试者工作特征(ROC)曲线下面积(AOC)作为诊断指标，并用随机分组试验数据进行验证。结直肠癌、乳腺癌患者和健康对照组的血浆氨基酸谱不同。没有观察到任何癌症患者的体重下降。每个判别分数的判别ROC曲线的AUC值分别为：结直肠癌0.863，乳腺癌0.856。使用拆分测试数据观察到可重复性的性能。此外，这些判别式的表现与癌症分期无关。癌症的发生改变了血浆氨基酸谱，而没有恶病质或体重下降，而且不同癌症的变化模式不同。因此，血浆氨基酸图谱可能有助于几种癌症的低成本早期检测。

The amino-acid balance is altered in patients with various diseases, due to metabolic changes. The metabolism in cancer cells is also known to be notably altered. Amino-acid profiles could therefore be useful biomarkers of various cancers. In this study, significant changes of amino-acid profiles were detected in the plasma of colorectal and breast cancer patients through multivariate analysis.Venous blood samples were taken from colorectal cancer patients, breast cancer patients, and healthy controls. Plasma free amino acids were measured by liquid chromatography(LC)/mass spectrometry(MS). Based on the amino-acid profiles, multiple logistic-regression models were used to discriminate between colorectal or breast cancer patients and control subjects. Diagnostic performance was evaluated as the area under the curve(AOC) of the receiver operating characteristic(ROC) curve, and was validated with randomly divided test data.The plasma amino-acid profiles differed between colorectal and breast cancer patients and healthy controls. No weight loss was observed in any of the cancer patients. The AUC of the discriminant ROC curve for each discriminant score was calculated as 0.863 for colorectal cancer and 0.856 for breast cancer. Reproducible performance was observed using split test data. Moreover, the performance of these discriminants was independent of the cancer stage.The occurrence of cancer alters plasma amino-acid profiles without cachexia or weight loss, and the pattern of change differs between cancers. Plasma amino-acid profiling might therefore be useful for the low-cost early detection of several kinds of cancer.