Stonāns Ilmārs, Kuzmina Jelizaveta, Poļaka Inese, Grīnberga Solveiga, Sevostjanovs Eduards, Liepiņš Edgars, Aleksandraviča Ilona, Šantare Daiga, Kiršners Arnis, Škapars Roberts, Pčolkins Andrejs, Tolmanis Ivars, Sīviņš Armands, Leja Mārcis, Dambrova Maija
Institute of Clinical and Preventive Medicine, University of Latvia, LV-1079 Riga, Latvia.
Mass Spectrometry Group, Latvian Institute of Organic Synthesis, LV-1006 Riga, Latvia.
Diagnostics (Basel). 2023 Apr 4;13(7):1341. doi: 10.3390/diagnostics13071341.
Our study aimed to evaluate the association between gastric cancer (GC) and higher concentrations of the metabolites L-carnitine, γ-butyrobetaine (GBB) and gut microbiota-mediated trimethylamine N-oxide (TMAO) in the circulation. There is evidence suggesting that higher levels of TMAO and its precursors in blood can be indicative of either a higher risk of malignancy or indeed its presence; however, GC has not been studied in this regard until now. Our study included 83 controls without high-risk stomach lesions and 105 GC cases. Blood serum L-carnitine, GBB and TMAO levels were measured by ultra-high-performance liquid chromatography-mass spectrometry (UPLC/MS/MS). Although there were no significant differences between female control and GC groups, we found a significant difference in circulating levels of metabolites between the male control group and the male GC group, with median levels of L-carnitine reaching 30.22 (25.78-37.57) nmol/mL vs. 37.38 (32.73-42.61) nmol/mL ( < 0.001), GBB-0.79 (0.73-0.97) nmol/mL vs. 0.97 (0.78-1.16) nmol/mL ( < 0.05) and TMAO-2.49 (2.00-2.97) nmol/mL vs. 3.12 (2.08-5.83) nmol/mL ( < 0.05). Thus, our study demonstrated the association between higher blood levels of L-carnitine, GBB, TMAO and GC in males, but not in females. Furthermore, correlations of any two investigated metabolites were stronger in the GC groups of both genders in comparison to the control groups. Our findings reveal the potential role of L-carnitine, GBB and TMAO in GC and suggest metabolic differences between genders. In addition, the logistic regression analysis revealed that the only significant factor in terms of predicting whether the patient belonged to the control or to the GC group was the blood level of L-carnitine in males only. Hence, carnitine might be important as a biomarker or a risk factor for GC, especially in males.
我们的研究旨在评估胃癌（GC）与循环中代谢物L-肉碱、γ-丁甜菜碱（GBB）以及肠道微生物群介导的氧化三甲胺（TMAO）浓度升高之间的关联。有证据表明，血液中较高水平的TMAO及其前体可能表明恶性肿瘤风险较高或确实存在恶性肿瘤；然而，迄今为止尚未在这方面对胃癌进行研究。我们的研究纳入了83名无高危胃部病变的对照者和105例胃癌患者。采用超高效液相色谱-质谱联用仪（UPLC/MS/MS）测定血清L-肉碱、GBB和TMAO水平。虽然女性对照组和胃癌组之间没有显著差异，但我们发现男性对照组和男性胃癌组之间循环代谢物水平存在显著差异，L-肉碱的中位数水平分别为30.22（25.78 - 37.57）nmol/mL和37.38（32.73 - 42.61）nmol/mL（<0.001），GBB为0.79（0.73 - 0.97）nmol/mL和0.97（0.78 - 1.16）nmol/mL（<0.05），TMAO为2.49（2.00 - 2.97）nmol/mL和3.12（2.08 - 5.83）nmol/mL（<0.05）。因此，我们的研究证明了男性血液中较高水平的L-肉碱、GBB、TMAO与胃癌之间存在关联，而女性则不然。此外，与对照组相比，两种性别的胃癌组中任意两种研究代谢物之间的相关性更强。我们的研究结果揭示了L-肉碱、GBB和TMAO在胃癌中的潜在作用，并表明了性别之间的代谢差异。此外，逻辑回归分析显示，在预测患者属于对照组还是胃癌组方面，唯一显著的因素仅是男性血液中L-肉碱的水平。因此，肉碱可能作为胃癌的生物标志物或危险因素具有重要意义，尤其是在男性中。
