外周T细胞淋巴瘤患者血清代谢产物与临床特征的相关性分析  

Correlation of serum metabolites and clinical features in patients with peripheral T-cell lymphoma

作　　者：段一硕 饶军 夏菁 马娜丫 蔺诗佳 李甫 唐书翰 周沙 曾韫璟 李炘檑 黄德智 李琼 刘帮洞 赵先兰 魏锦[1] 张曦 DUAN Yishuo;RAO Jun;XIA Jing;MA Naya;LIN Shijia;LI Fu;TANG Shuhan;ZHOU Sha;ZENG Yunjing;LI Xinlei;HUANG Dezhi;LI Qiong;LIU Bangdong;ZHAO Xianlan;WEI Jin;ZHANG Xi(Department of Hematology,Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan Province,637002;State Key Laboratory of Trauma and Chemical Poisoning,Medical Center of Hematology,Military Key Clinical Specialty,Chongqing Key Clinical Specialty,Chongqing Key Laboratory of Hematology and Microenvironment,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400037;Jinfeng Laboratory,Chongqing,401329,China)

机构地区：[1]川北医学院附属医院血液内科,南充637002 [2]陆军军医大学(第三军医大学)第二附属医院血液病医学中心,全军临床重点专科,创伤与化学中毒全国重点实验室,重庆市临床重点专科,血液病与微环境重庆市重点实验室,重庆400037 [3]金凤实验室,重庆401329

出　　处：《陆军军医大学学报》2024年第4期352-358,共7页Journal of Army Medical University

基　　金：国家自然科学基金面上项目(82070208)。

摘　　要：目的 观察外周T细胞淋巴瘤患者血清能量代谢产物的变化,从能量代谢角度寻找监测外周T细胞淋巴瘤的血清生物标志物。方法 收集2020年11月至2021年12月在陆军军医大学第二附属医院血液病医学中心诊治的16例外周T细胞淋巴瘤初诊患者,并招募同期10名健康志愿者作为对照。采用选择性反应/多反应监测技术(selected/multiple reaction monitoring, SRM/MRM)检测其血清中能量相关代谢产物的差异,并结合其临床资料,包括病史、影像学、实验室检查等进行回顾性分析。结果 与健康对照相比,外周T细胞淋巴瘤患者血清中能量代谢相关产物水平表达谱存在差异,其中环磷腺苷、琥珀酸、柠檬酸和顺乌头酸含量显著降低(P<0.05),6-磷酸葡萄糖水平升高(P<0.05),且患者血清中的柠檬酸和琥珀酸水平与疾病危险度分级(低危、中危、高危)和临床分期呈负相关(P<0.05),同时,苹果酸和柠檬酸水平与患者中期疗效评估结果[完全缓解/部分缓解(CR/PR)或疾病稳定(SD)]呈明显负相关(P<0.05)。对于结外NK/T细胞淋巴瘤患者(n=10),与健康对照相比,其血清中环磷腺苷、琥珀酸、柠檬酸、异柠檬酸和顺乌头酸含量亦有显著降低(P<0.05),其中柠檬酸与琥珀酸的水平与结外NK/T细胞淋巴瘤患者的临床分期呈负相关(P<0.05),与中期疗效评估(CD/PR或SD)呈明显相关性(P<0.05);对于血管免疫母细胞性T细胞淋巴瘤患者(n=6),与健康对照相比,其血清中环磷腺苷、柠檬酸和琥珀酸的含量明显降低,而6-磷酸葡萄糖的含量明显升高(P<0.05),其中琥珀酸水平分别与患者临床分期和危险度分级都表现出明显的负相关(P<0.05)。结论 外周T细胞淋巴瘤患者与健康对照人群在血清代谢产物水平上共鉴定出5个差异代谢产物,其中琥珀酸、柠檬酸有希望成为血清生物标志物。Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P<0.05),and elevated D-glucose 6-phosphate content(P<0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P<0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P<0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P<0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P<0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P<0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was highe

关 键 词：外周T细胞淋巴瘤 结外NK/T细胞淋巴瘤 血管免疫母细胞性T细胞淋巴瘤 血清代谢组学 生物标志物 多反应监测 

分 类 号：R181.32[医药卫生—流行病学] R446.112[医药卫生—公共卫生与预防医学] R733.4