口腔鳞状细胞癌的血清生物标志物鉴定及代谢紊乱特征研究  

Identification of serum biomarkers and evaluation of metabolism disorders in patients with oral squamous cell carcinoma

作　　者：李希博 刘丽伟 李娜[1] 贾清泉 王晓霜 龙江兰 薛鹏[5] 孙志[2] 赵红宇[1] Li Xibo;Liu Liwei;Li Na;Jia Qingquan;Wang Xiaoshuang;Long Jianglan;Xue Peng;Sun Zhi;Zhao Hongyu(Department of Oral Emergency,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Pharmacy,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine,Zhengzhou 450052,China;Beijing Key Laboratory and Joint Laboratory for International Cooperation of Bio-characteristic Profiling for Evaluation of Rational Drug Use,Capital Medical University Affiliated Beijing Shijitan Hospital,Beijing 100038,China;Health Management Center,The First Affiliated Hospital of Zhengzhou Unversity,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院口腔急诊科,450052 [2]郑州大学第一附属医院药学部,450052 [3]河南省精准医学临床质谱工程研究中心,郑州450052 [4]首都医科大学附属北京世纪坛医院临床合理用药生物特征谱学评价北京市重点实验室,100038 [5]郑州大学第一附属医院健康管理中心,450052

出　　处：《中华口腔医学杂志》2021年第9期926-932,共7页Chinese Journal of Stomatology

基　　金：河南省高等学校重点科研项目计划(21A320025);河南省医学科技攻关计划省部共建项目(SBGJ202002116);北京康盟医学科研发展基金(TB204022)。

摘　　要：目的探讨口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)的代谢紊乱特征,并发现和鉴定OSCC的生物标志物,为其早期诊断提供新思路。方法本研究共纳入2019年8月至2020年1月就诊于郑州大学第一附属医院口腔颌面外科的76例OSCC患者和体检科的70名健康受试者,按照随机数表法按2∶1的比例将所有受试者分为测试组和验证组,测试组共96例受试者,其中OSCC患者51例,健康受试者45名;验证组共50例受试者,其中OSCC患者25例,健康受试者25名。收集所有受试者的血液样本及临床资料,基于超高效液相色谱-四极杆/静电场轨道阱高分辨质谱技术建立血清样本非靶向代谢组学分析方法,进一步结合主成分分析、偏正交最小二乘法判别分析和t检验分析发现并鉴定测试组中OSCC患者和健康受试者之间的差异代谢物,并对得到的差异代谢物进行代谢通路分析。二元Logistic回归分析和受试者工作特征曲线分析用以进一步筛选和确定OSCC的生物标志物,构建OSCC诊断模型,用验证组检验诊断模型的诊断效能。结果对比分析测试组中OSCC患者和健康受试者的血清样本后得到21种内源性差异代谢物,代谢通路分析提示OSCC患者存在脂质代谢和氨基酸代谢紊乱(P<0.05)。本研究构建了由溶血磷脂酰胆碱(lysophosphatidylcholine,LysoPC)(16∶0/0∶0)、LysoPC[18∶1(9Z)/0∶0]、牛磺酸和D-谷氨酸组成的诊断模型(曲线下面积为0.998,95%CI为0.994~0.999,P<0.05)。结论OSCC患者体内发生了明显的脂质和氨基酸代谢紊乱,代谢组学手段是建立OSCC诊断模型的有效方法。Objective To explore the changes in serum metabolic profile in patients with oral squamous cell carcinoma(OSCC)and to identify the diagnostic biomarkers in order to provide new ideas for the early diagnosis of OSCC.Methods In total,76 OSCC patients who were diagnosed at the Department of Oral and Maxillofacial Surgery and 70 healthy individuals who at the Department of Medical Center of The First Affiliated Hospital of Zhengzhou University from August 2019 to January 2020 were recruited in The study.According to the random number table method,all subjects were divided into a test group(n=96)and a verification group(n=50).Subjects in the test group consisted of 51 OSCC patients and 45 healthy subjects and subjects in the verification group included 25 OSCC patients and 25 healthy individuals.Serum samples and clinical data of each of the subjects were collected.The serum samples were analyzed by ultra-high-performance liquid chromatography quadrupole-Orbitrap high resolution accurate mass spectrometry.Principal component analysis,orthogonal partial least square discrimination analysis and t-test were used to profile the differential metabolites in the test group.Pathway analysis of differential metabolites was performed.In addition,binary logistic regression analysis and receiver operating characteristic analysis were used in order to establish the potential diagnostic panel.Results Twenty-one endogenous differential metabolites were identified showing significant association with OSCC.Results of pathway analysis suggested that OSCC associated with lipid metabolism and amino acid metabolism(P<0.05).A novel diagnostic panel consisting of lysophosphatidylcholine(LysoPC)(16∶0/0∶0),LysoPC[18∶1(9z)/0∶0],taurine and D-glutamic acid was defined.The panel performed a high area under the receiver operating characteristic curve(0.998,95%CI:0.994-0.999,P<0.05).Conclusions There were obvious lipid and amino acid metabolism disorders in OSCC patients.It was an effective method to establish a diagnostic model by metabol

关 键 词：癌 鳞状细胞 代谢组学 生物标志物 代谢紊乱 诊断 

分 类 号：R739.8[医药卫生—肿瘤]