National Leading Research Laboratory of Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, College of Human Ecology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Institute for Health Promotion, Graduate School of Public Health, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Metabolomics. 2022 Jul 28;18(8):62. doi: 10.1007/s11306-022-01922-7.
Monitoring metabolic biomarkers could be utilized as an effective tool for the early detection of gastric cancer (GC) risk.
We aimed to discover predictive serum biomarkers for GC and investigate biomarker-related metabolism.
Subjects were randomly selected from the Korean Cancer Prevention Study-II cohort and matched by age and sex. We analyzed baseline serum samples of 160 subjects (discovery set; control and GC occurrence group, 80 each) via nontargeted screening. Identified putative biomarkers were validated in baseline serum samples of 140 subjects (validation set; control and GC occurrence group, 70 each) using targeted metabolites analysis.
The final analysis was conducted on the discovery set (control, n = 52 vs. GC occurrence, n = 50) and the validation set (control, n = 43 vs. GC occurrence, n = 44) applying exclusion conditions. Eighteen putative metabolite sets differed between two groups found on nontargeted metabolic screening. We focused on fatty acid-related energy metabolism. In targeted analysis, levels of decanoyl-L-carnitine (p = 0.019), L-carnitine (p = 0.033), and citric acid (p = 0.025) were significantly lower in the GC occurrence group, even after adjusting for age, sex, and smoking status. Additionally, L-carnitine and citric acid were confirmed to have an independently significant relationship to GC development. Notably, alkaline phosphatase showed a significant correlation with these two biomarkers.
Changes in serum L-carnitine and citric acid levels that may result from alterations of fatty-acid-related energy metabolism are expected to be valuable biomarkers for the early diagnosis of GC risk.
监测代谢生物标志物可作为早期发现胃癌(GC)风险的有效工具。
我们旨在发现预测 GC 的血清生物标志物,并研究生物标志物相关代谢。
从韩国癌症预防研究-II 队列中随机选择受试者,并按年龄和性别进行匹配。我们通过非靶向筛选分析了 160 名受试者(发现组;对照组和 GC 发生组,每组 80 名)的基线血清样本。使用靶向代谢物分析在 140 名受试者(验证组;对照组和 GC 发生组,每组 70 名)的基线血清样本中验证了鉴定出的候选生物标志物。
最终分析应用排除条件后在发现组(对照组,n=52 例 vs. GC 发生组,n=50 例)和验证组(对照组,n=43 例 vs. GC 发生组,n=44 例)中进行。非靶向代谢筛选发现两组之间有 18 个候选代谢物组存在差异。我们关注与脂肪酸相关的能量代谢。在靶向分析中,癸酰基肉碱(p=0.019)、肉碱(p=0.033)和柠檬酸(p=0.025)的水平在 GC 发生组中显著降低,即使在调整年龄、性别和吸烟状况后也是如此。此外,肉碱和柠檬酸被证实与 GC 发生有独立的显著关系。值得注意的是,碱性磷酸酶与这两种生物标志物有显著相关性。
血清肉碱和柠檬酸水平的变化可能是由于脂肪酸相关能量代谢的改变引起的,这些变化有望成为 GC 风险早期诊断的有价值的生物标志物。