Simancas-Escorcia Víctor, Plazas-Román Jaime, Díaz-Caballero Antonio, Martínez-Martínez Adel, Ardila Carlos M
GENOMA Research Group, Universidad del Sinú, Cartagena Section, Cartagena, Colombia.
GITOUC Research Group, Faculty of Dentistry, Universidad de Cartagena, Cartagena, Colombia.
Odontology. 2025 Sep 10. doi: 10.1007/s10266-025-01194-2.
Orthodontic-induced gingival enlargement (OIGE) affects approximately 15-30% of patients undergoing orthodontic treatment and remains largely unpredictable, often relying on subjective clinical assessments made after irreversible tissue changes have occurred. S100A4 is a well-characterized marker of activated fibroblasts involved in pathological tissue remodeling. This was a cross-sectional precision biomarker study that analyzed gingival tissue samples from three groups: healthy controls (n = 60), orthodontic patients without gingival enlargement (n = 31), and patients with clinically diagnosed OIGE (n = 61). Immunohistochemical analysis quantified S100A4-positive fibroblasts, type I collagen synthesis, and microvascular density. Advanced statistical analyses included multivariate logistic regression, machine learning-based validation, causal mediation analysis, and survival modeling for risk stratification. The density of S100A4-positive fibroblasts was significantly higher in OIGE patients (245.8 ± 38.7 cells/mm) compared to orthodontic controls (165.3 ± 29.4 cells/mm) and healthy individuals (98.2 ± 18.5 cells/mm) (p < 0.001; η = 0.891). Multivariate analysis confirmed S100A4 as an independent predictor of OIGE (OR = 1.028 per cell/mm; 95%CI 1.021-1.035; p < 0.001). Machine learning validation demonstrated high predictive accuracy (AUC = 0.946). Survival analysis identified distinct risk strata: individuals with S100A4 densities > 180 cells/mm had a 78% probability of developing OIGE within 24 months, compared to 12% for those with < 130 cells/mm. S100A4 demonstrates 95% predictive accuracy for OIGE, supporting its role in personalized risk stratification and early preventive interventions during a defined therapeutic window. This study presents the first validated precision biomarker in orthodontics with the potential to prevent an estimated 180,000-360,000 OIGE cases globally each year.
正畸诱导性牙龈增生（OIGE）影响约15%-30%接受正畸治疗的患者，且很大程度上仍不可预测，通常依赖于在不可逆组织变化发生后进行的主观临床评估。S100A4是参与病理性组织重塑的活化成纤维细胞的一个特征明确的标志物。这是一项横断面精确生物标志物研究，分析了三组牙龈组织样本：健康对照组（n = 60）、无牙龈增生的正畸患者（n = 31）和临床诊断为OIGE的患者（n = 61）。免疫组织化学分析对S100A4阳性成纤维细胞、I型胶原合成和微血管密度进行了量化。先进的统计分析包括多变量逻辑回归、基于机器学习的验证、因果中介分析和用于风险分层的生存建模。与正畸对照组（165.3±29.4个细胞/mm）和健康个体（98.2±18.5个细胞/mm）相比，OIGE患者中S100A4阳性成纤维细胞的密度显著更高（245.8±38.7个细胞/mm）（p < 0.001；η = 0.891）。多变量分析证实S100A4是OIGE的独立预测因子（每细胞/mm的OR = 1.028；95%CI 1.021-1.035；p < 0.001）。机器学习验证显示出高预测准确性（AUC = 0.946）。生存分析确定了不同的风险分层：S100A4密度>180个细胞/mm的个体在24个月内发生OIGE的概率为78%，而密度<130个细胞/mm的个体为12%。S100A4对OIGE的预测准确性达95%，支持其在个性化风险分层和在确定的治疗窗口期内进行早期预防性干预中的作用。本研究提出了正畸学中首个经过验证的精确生物标志物，每年有可能在全球预防约180,000-360,000例OIGE病例。
