Belpomme Dominique, Lacomme Stéphanie, Poletti Clément, Bonesso Laurent, Hinault-Boyer Charlotte, Barbier Sylvie, Irigaray Philippe
Department of Cancer Clinical Research, Paris V University Hospital, 75005 Paris, France.
European Cancer and Environment Research Institute (ECERI), 1000 Brussels, Belgium.
Cancers (Basel). 2024 Nov 22;16(23):3922. doi: 10.3390/cancers16233922.
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.
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.
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 ( < 0.0001), and similar to those in the peripheral blood of hyperglycemic diabetic patients ( = 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 ( < 0.0001), and is subsequently released in the peripheral blood.
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.
癌细胞的一个基本特性是其代谢重编程,这使得它们能够增加葡萄糖摄取和糖酵解。我们之前使用大鼠结肠腺癌模型表明,糖酵解副产物游离甲基乙二醛(MG)的血液水平在移植了不生长肿瘤细胞克隆的动物中保持正常,而在移植了源自同一肿瘤的致瘤细胞克隆的动物中,MG水平显著升高且与肿瘤生长呈正相关。
我们测量了癌症非糖尿病患者血液中的游离MG,并将结果与健康受试者和非癌症糖尿病患者进行比较。我们还测量了肿瘤及其相应非癌组织以及外周血中的游离MG。
我们发现,与健康对照者外周血中的游离MG水平相比,癌症患者外周血中的游离MG水平显著升高(<0.0001),且与高血糖糖尿病患者外周血中的游离MG水平相似(=0.965)。此外,我们表明重复测量游离MG水平可用于癌症患者的治疗监测。而且,我们证实肿瘤细胞产生游离MG的水平显著高于其相应组织中的细胞(<0.0001),随后游离MG被释放到外周血中。
血液中检测到的游离MG可能是一种新的代谢生物标志物,对支气管癌、胰腺癌和胶质母细胞瘤等目前尚无可用有效生物标志物的非糖尿病癌症患者的诊断、预后评估及随访具有重要意义。