基于龈沟液蛋白质组学的正畸牙根外吸收早期生物标志物筛选及鉴定

doi:10.13701/j.cnki.kqyxyj.2026.09.006

口腔医学研究 ›› 2026, Vol. 42 ›› Issue (9): 764-770.DOI: 10.13701/j.cnki.kqyxyj.2026.09.006

基于龈沟液蛋白质组学的正畸牙根外吸收早期生物标志物筛选及鉴定

何佳玥^1,2, 陈诗曼^1,2, 刘钰昕^1,2, 李跞鑫^1,2, 沈玉凤^1*, 周政^1*

1.石河子大学第一附属医院口腔科新疆石河子 832008;
2.石河子大学临床医学院新疆石河子 832003

收稿日期:2025-12-03 出版日期:2026-09-28 发布日期:2026-09-22
通讯作者: * 沈玉凤,E-mail:15909932233@163.com周政,E-mail:15909935188@163.com
作者简介:何佳玥(1999~ ),女,新疆石河子人,硕士,住院医师,研究方向:口腔正畸学。
基金资助:
中华口腔医学会西部口腔医学临床科研基金项目(编号:CSA-W2024-04);石河子大学第一附属医院博士课题基金项目(编号:BS2023003);国家自然科学基金青年科学基金(编号:82401172);兵团科技计划青年科学项目(编号:2025DB040)

Screening and Identification of Early Biomarkers for Orthodontic External Apical Root Resorption via Gingival Crevicular Fluid Proteomics

HE Jiayue^1,2, CHEN Shiman^1,2, LIU Yuxin^1,2, LI Luoxin^1,2, SHEN Yufeng^1*, ZHOU Zheng^1*

1. Department of Stomatology, The First Affiliated Hospital of Shihezi University, Shihezi 832008, China;
2. Clinical Medical College of Shihezi University, Shihezi 832003, China

Received:2025-12-03 Online:2026-09-28 Published:2026-09-22

摘要/Abstract

摘要： 目的:探讨正畸牙根外吸收(external apical root resorption,EARR)的早期诊断生物标志物,为临床早期预警提供分子依据。方法:本研究共纳入15例经临床及影像学确诊的EARR患者,并收集其龈沟液样本。利用数据非依赖采集(data-independent acquisition, DIA)蛋白质组学技术进行蛋白分析,结合LASSO回归机器学习算法筛选关键蛋白,并通过酶联免疫吸附试验法(enzyme-linked immunosorbent assay, ELISA)与Western blot在临床样本及成牙骨质细胞OCCM-30力学模型中对关键蛋白进行实验验证。结果:共鉴定出759种蛋白质,其中51个为差异表达蛋白。基于机器学习算法确定S100钙结合蛋白A2(S100 calcium binding protein A2, S100A2)、S100钙结合蛋白A9(S100 calcium binding protein A9, S100A9)和钙蛋白酶2(calpain 2, CAPN2)为关键枢纽蛋白。受试者操作特征(receiver operating characteristic, ROC)曲线分析表明,三者均具有良好的诊断区分能力[曲线下面积(area under the curve, AUC)>0.7]。ELISA与Western blot实验结果进一步证实,在T1期及体外加压条件下,S100A2、S100A9和CAPN2的表达均显著上调 (P<0.05)。结论:S100A2、S100A9和CAPN2是EARR潜在的早期诊断生物标志物,其表达受机械应力调控,可能参与炎症激活和细胞结构破坏过程,为EARR的无创监测与临床防治提供分子基础。

关键词: 正畸牙根外吸收, 龈沟液, 蛋白质组学, 生物标志物, 机器学习

Abstract: Objective: To explore early diagnostic biomarkers for orthodontic external apical root resorption (EARR) and provide a molecular basis for early clinical warning. Methods: The study included 15 patients clinically and radiographically confirmed with orthodontic EARR, and their gingival crevicular fluid samples were collected. Data-independent acquisition (DIA) proteomics technology was employed for protein analysis. Key proteins were screened by combining LASSO regression machine learning algorithms. The identified key proteins were experimentally validated in clinical samples and in a mechanical stress model using osteocementum-like cells OCCM-30 via enzyme-linked immunosorbent assay (ELISA) and Western blot. Results: A total of 759 proteins were identified, among which 51 were differentially expressed proteins. Based on the machine learning algorithms, S100 calcium binding protein A2 (S100A2), S100 calcium binding protein A9 (S100A9), and Calpain 2 (CAPN2) were identified as key hub proteins. Receiver operating characteristic (ROC) curve analysis demonstrated that all three proteins possessed good diagnostic discriminatory capability [area under the curve (AUC)>0.7]. ELISA and Western blot results further confirmed that the expression levels of S100A2, S100A9, and CAPN2 were significantly upregulated at the T1 stage and under in vitro compressive conditions (P<0.05). Conclusion: S100A2, S100A9, and CAPN2 are potential early diagnostic biomarkers for EARR. Their expression is regulated by mechanical stress and they may be involved in processes such as inflammatory activation and cellular structure disruption. This study provides a molecular basis for the non-invasive monitoring and clinical prevention management of EARR.

Key words: orthodontically induced external apical root resorption, gingival crevicular fluid, proteomics, biomarkers, machine learning

何佳玥, 陈诗曼, 刘钰昕, 李跞鑫, 沈玉凤, 周政. 基于龈沟液蛋白质组学的正畸牙根外吸收早期生物标志物筛选及鉴定[J]. 口腔医学研究, 2026, 42(9): 764-770.

HE Jiayue, CHEN Shiman, LIU Yuxin, LI Luoxin, SHEN Yufeng, ZHOU Zheng. Screening and Identification of Early Biomarkers for Orthodontic External Apical Root Resorption via Gingival Crevicular Fluid Proteomics[J]. Journal of Oral Science Research, 2026, 42(9): 764-770.

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基于龈沟液蛋白质组学的正畸牙根外吸收早期生物标志物筛选及鉴定

Screening and Identification of Early Biomarkers for Orthodontic External Apical Root Resorption via Gingival Crevicular Fluid Proteomics

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