Establishing age-group specific reference intervals of human salivary proteome and its preliminary application for epilepsy diagnosis  

作　　者：Nianci Xue Xia Xia Yini Wang Xianju Li Nairen Zheng Yi Wang Baoying Gong Bin Zhang Yanjia Chen Yue Chen Yanjuan Li Hong Cao Wofeng Liu Hongqiang Huang Shuo Yang Lisen Sui Lin Meng Jianwen Guo Jun Qin 

机构地区：[1]State KeyLaboratoryofTraditionalChinese MedicineSyndrome,State KeyLaboratoryof DampnessSyndromeofChinese MedicineSyndrome,Departmentof Neurology,TheSecondary Affiliated Hospitalof Guangzhou University of Chinese Medicine,Guangdong Provincial Hospital of Chinese Medicine,Guangdong Provincial Academy of Chinese Medical Sciences,Guangzhou 510120,China [2]State Key Laboratory of Medical Proteomics,Beijing Proteome Research Center,National Center for Protein Sciences(Beijing),Beijing Institute of Lifeomics,Beijing 102206,China [3]Guangzhou University of Chinese Medicine,Guangzhou 510006,China [4]Guangdong Mechanical&Electrical Polytechnic,Guangzhou 510440,China [5]Guangzhou Cadre and Talent Health Management Center(Guangzhou 11th People’s Hospital),Guangzhou 510779,China [6]Department of epilepsy,The Secondary Hospital of Guangzhou University of Chinese Medicine,Guangdong Provincial Hospital of Traditional Chinese Medicine,Guangzhou 510120,China

出　　处：《Science China(Life Sciences)》2025年第3期809-824,共16页中国科学(生命科学英文版)

基　　金：supported by the National Natural Science Foundation of China(32088101,32271498);the National Key Research and Development Program of China(2022YFA1303200);State Key Laboratory of Proteomics(SKLP-K202002);State Key Laboratory of Dampness Syndrome of Chinese Medicine,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(SZ2021ZZ06,SZ2021ZZ3205);Key-Area Research and Development Program of Guangdong Province(2020B1111100009);Guangzhou Science and Technology Plan Project(202102010275,202201020499).

摘　　要：Salivary proteins serve multifaceted roles in maintaining oral health and hold significant potential for diagnosing and monitoring diseases due to the non-invasive nature of saliva sampling.However,the clinical utility of current saliva biomarker studies is limited by the lack of reference intervals(RIs)to correctly interpret the testing result.Here,we developed a rapid and robust saliva proteome profiling workflow,obtaining coverage of>1,200 proteins from a 50-μL unstimulated salivary flow with 30 min gradients.With the workflow,we investigated protein variation in a cohort of 1,743 healthy individuals.The significant differences in non-linear saliva proteomes among age groups resulted in the establishment of age-related RIs covering 1,123 salivary protein variations.We then utilized a cohort of 30 epilepsy patients as a case study to illustrate the practical application of RIs in identifying disease-enriched outlier proteins,elucidating their cellular origins,determining disease diagnosis,and visualizing outlier proteins in each epilepsy patient.Our study showed the classification model based on the RI achieved PR-AUC of 0.815(95%CI:0.813–0.826).Additionally,we validated these results in an independent test set.Furthermore,the epilepsy cohort could be further stratified into 2 major subtypes,with one subtype characterized by disrupted metabolic proteins and containing mostly Focal Cortical Dysplasia(FCD)type III epilepsy patients.Overall,our study provided a proof-of-principle workflow for the use of salivary proteome for health monitoring,epilepsy diagnosis and subtyping.

关 键 词：reference intervals saliva proteomics EPILEPSY biomarker disease subtypes 

分 类 号：R74[医药卫生—神经病学与精神病学]