琥珀酸脱氢酶基因 (SDHx) 种系致病变异 (PV) 携带者有患肿瘤的风险，包括副神经节瘤、胃肠道间质瘤和肾细胞癌。早期肿瘤检测对于改善临床结果至关重要。基于血液的生物标志物可以帮助早期识别患有PV的个体，并为具有未知意义的变异的患者提供功能证据。对患有和不患有SDHx PV的患者的血浆、尿液、外周血单核细胞和红细胞进行了中心碳代谢物的研究。这些通过液相色谱-串联质谱法和核磁共振波谱法进行测量，其中包括琥珀酸盐、富马酸盐、α-酮戊二酸盐和乳酸盐。血浆琥珀酸盐与富马酸盐的比率有效地区分患有和不患有SDHx PV的荷瘤患者和无症状患者尽管 SDHB PV 个体的水平较高，但诊断性能有希望（受试者工作特征曲线下面积为 0.86-0.95）。尿液和外周血单核细胞提取物中的代谢物在各组之间基本相似。与对照组相比，SDHx PV 患者的红细胞表现出强烈的代谢变化，13 种低分子有机酸中有 8 种存在显着差异 (P < .05)。红细胞的乳酸-α-酮戊二酸比率对 SDHx PV 个体的识别效果与血浆相同，敏感性和特异性均为 92% (AUC 0.97)。血液生物标志物在识别 SDHx PV 携带者或验证未知变异体方面尚未得到充分利用。意义。我们的研究结果主张进一步研究涉及血浆和红细胞的联合方法，以用于未来的诊断策略。© 作者 2024。由牛津大学出版社代表内分泌学会出版。

Carriers of germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx) are at risk of developing tumors, including paragangliomas, gastrointestinal stromal tumors, and renal cell carcinomas. Early tumor detection is paramount for improved clinical outcome. Blood-based biomarkers could aid in identifying individuals with PVs early and provide functional evidence in patients with variants of unknown significance.Blood plasma, urine, peripheral blood mononuclear cells, and erythrocytes from patients with and without SDHx PVs were investigated for central carbon metabolites. These were measured by liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy and included among others, succinate, fumarate, α-ketoglutarate, and lactate.Plasma succinate to fumarate ratios effectively distinguished tumor-bearing and asymptomatic patients with and without SDHx PV with promising diagnostic performance (areas under the receiver operating characteristic curve 0.86-0.95), although higher levels were noted in individuals with SDHB PV. Metabolites in urine and in peripheral blood mononuclear cell extracts were largely similar between groups. Erythrocytes showed strong metabolic alterations in patients with SDHx PV compared to controls, with 8 of 13 low-molecular organic acids being significantly different (P < .05). The lactate-α-ketoglutarate-ratio of erythrocytes identified individuals with SDHx PV equally well as plasma, with a sensitivity and specificity of 92% (AUC 0.97).Blood biomarkers have been underutilized for identifying carriers of SDHx PV or to validate variants of unknown significance. Our findings advocate for further investigation into a combined approach involving plasma and erythrocytes for future diagnostic strategies.© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.