Background: A fundamental property of cancer cells is their metabolic reprogramming, allowing them to increase glucose uptake and glycolysis. Using a rat colon adenocarcinoma model, we previously showed that blood levels of free methylglyoxal (MG), a side-product of glycolysis, remained normal in animals grafted with a non-growing tumor cell clone, while MG levels were significantly increased and positively correlated with tumor growth in animals grafted with a tumorigenic cell clone issued from the same tumor. Methods: We measured free MG in the blood of cancerous non-diabetic patients and compared the results to healthy subjects and non-cancerous diabetic patients. We also measured free MG in tumors and in the corresponding non-cancer tissues, and the peripheral blood. Results: We show that free MG levels in the peripheral blood of cancer patients are significantly increased in comparison with free MG levels in the peripheral blood of healthy controls (p< 0.0001), and similar to those in the peripheral blood of hyperglycemic diabetic patients (p= 0.965). In addition, we show that repeated free MG level measurement could be used for the therapeutic monitoring of cancer patients. Moreover, we confirmed that free MG is produced by tumor cells at significantly higher levels than cells from their corresponding tissues (p< 0.0001), and is subsequently released in the peripheral blood. Conclusions: Free MG measured in the blood could be a new metabolic biomarker useful for the diagnostic, prognostic and follow-up of non-diabetic patients with cancers, such as bronchus carcinoma, pancreatic carcinoma and glioblastoma, for which there are presently no available useful biomarkers.
背景：癌细胞的一个基本特性是其代谢重编程，使其能够增加葡萄糖摄取和糖酵解。通过大鼠结肠腺癌模型，我们先前发现，在移植了非生长性肿瘤细胞克隆的动物体内，血液中游离甲基乙二醛（糖酵解副产物）水平保持正常；而在移植了来自同一肿瘤的致瘤性细胞克隆的动物体内，MG水平显著升高，并与肿瘤生长呈正相关。方法：我们测量了非糖尿病癌症患者血液中的游离MG，并将结果与健康受试者及非癌症糖尿病患者进行比较。同时，我们还检测了肿瘤组织、对应非癌组织及外周血中的游离MG水平。结果：我们发现，癌症患者外周血中游离MG水平显著高于健康对照组（p<0.0001），而与高血糖糖尿病患者外周血中的水平相似（p=0.965）。此外，重复测量游离MG水平可用于癌症患者的治疗监测。更重要的是，我们证实肿瘤细胞产生的游离MG水平显著高于对应正常组织细胞（p<0.0001），并随后释放到外周血中。结论：血液中游离MG的检测可能成为一种新型代谢生物标志物，可用于非糖尿病癌症患者（如支气管癌、胰腺癌和胶质母细胞瘤）的诊断、预后评估及随访监测，这些癌症目前尚缺乏有效的生物标志物。
Free Methylglyoxal as a Metabolic New Biomarker of Tumor Cell Proliferation in Cancers
肿瘤(癌症)患者之家