白色念珠菌促进口腔白斑恶性进展的临床队列与动物模型初步研究OA
Candida albicans promotes malignant progression of oral leukoplakia:a preliminary study based on clinical cohort and animal models
目的 探究白色念珠菌与口腔白斑病(oral leukoplakia,OLK)发展的相关性,为完善OLK恶性转化的致病机制提供依据.方法 利用公共数据库(NCBI BioProject,PRJNA788378;GEO,GSE227919)获得口腔相关微生物组学数据,采用生物信息学方法评估白色念珠菌感染与OLK的相关性.获得单位医学伦理委员会批准,收集 OLK临床队列样本构建组织芯片,进行苏木精-伊红(hematoxylin and eosin,H&E)染色和过碘酸-Schiff(periodic acid-Schiff,PAS)染色,分析白色念珠菌检出率与临床病理特征之间的关系.获得单位实验动物伦理委员会批准,建立4-硝基喹啉-1-氧化物(4-nitroquinoline-1-oxide,4NQO)饮水联合白色念珠菌口腔接种的小鼠模型(4NQO+白色念珠菌组),以4NQO饮水并给予PBS处理作为对照组(4NQO+PBS组),比较两组上皮异常增生程度,评估白色念珠菌感染对病变进展的影响(本研究将高级别衍进定义为病变由轻/中度上皮异常增生向重度异常增生/原位癌乃至浸润性鳞状细胞癌发展的过程).结果 生物信息学分析显示,与健康对照组相比,口腔潜在恶性疾患(oral potentially malignant disorders,OPMDs)及OLK组织中白色念珠菌检出率显著升高.临床样本染色结果发现白色念珠菌可在OLK病灶中定植,相对于白色念珠菌阴性患者,阳性患者为更高级别衍进状态.动物实验表明,与4NQO+PBS组相比,4NQO+白色念珠菌组小鼠口腔上皮异常增生程度显著加重,恶性转化率更高,提示白色念珠菌可促进OLK向高级别衍进.结论 白色念珠菌在口腔白斑癌变衍进过程中呈升高趋势,可加重OLK上皮异常增生程度,促进其向高级别病变转化,提示白色念珠菌在OLK高级别衍进过程中发挥重要促进作用.
Objective To explore the correlation between Candida albicans and the development of oral leukopla-kia(OLK),and to provide a basis for improving the pathogenic mechanism of the malignant transformation of OLK.Methods Oral microbiome data were obtained from public databases(NCBI BioProject,PRJNA788378;GEO,GSE227919),and bioinformatic methods were employed to evaluate the correlation between Candida albicans infection and OLK.Approval was obtained from the institutional Medical Ethics Committee.A tissue microarray was constructed using samples collected from an OLK clinical cohort.Hematoxylin and eosin(H&E)staining and periodic acid-Schiff(PAS)staining were performed to analyze the relationship between the Candida albicans detection rate and clinicopatho-logical features.Approval was obtained from the institutional Animal Ethics Committee.A mouse model was established by combining 4-nitroquinoline-1-oxide(4NQO)in drinking water with oral inoculation of Candida albicans(4NQO+Candida albicans group),while mice treated with 4NQO in drinking water and PBS served as the control group(4NQO+PBS group).The degree of epithelial dysplasia was compared between the two groups to assess the impact of Candida albicans infection on lesion progression(defined in this study as the progression from mild/moderate epithelial dysplasia to severe dysplasia/carcinoma in situ or invasive squamous cell carcinoma).Results Bioinformatic analysis revealed that the detection rate of Candida albicans in OPMDs and OLK tissues was significantly higher than that in the healthy control group.Staining results of clinical samples demonstrated that Candida albicans colonized OLK lesions;compared with Candida albicans-negative patients,positive patients exhibited a state of high-grade progression.Animal experi-ments indicated that,compared with the 4NQO+PBS group,the degree of oral epithelial dysplasia in the 4NQO+Can-dida albicans group was significantly exacerbated,and the malignant transformation rate was higher,suggesting that Candida albicans promotes the high-grade progression of OLK.Conclusion Candida albicans exhibits a increasing trend during the malignant progression of the OLK.It aggravates the degree of epithelial dysplasia in OLK and pro-motes its transformation into high-grade lesions,suggesting that Candida albicans plays a crucial promoting role in the high-grade progression of OLK.
程方卜;张诗语;王影;李敬
口腔疾病防治全国重点实验室 国家口腔医学中心 口腔疾病国家临床医学研究中心 四川大学华西口腔医院基础医学系,四川 成都(610041)口腔疾病防治全国重点实验室 国家口腔医学中心 口腔疾病国家临床医学研究中心 四川大学华西口腔医院基础医学系,四川 成都(610041)口腔疾病防治全国重点实验室 国家口腔医学中心 口腔疾病国家临床医学研究中心 四川大学华西口腔医院基础医学系,四川 成都(610041)口腔疾病防治全国重点实验室 国家口腔医学中心 口腔疾病国家临床医学研究中心 四川大学华西口腔医院基础医学系,四川 成都(610041)
医药卫生
白色念珠菌口腔微生物口腔白斑病口腔潜在恶性疾患上皮异常增生口腔鳞状细胞癌生物信息学分析临床队列研究动物模型
Candida albicansoral microbiomeoral leukoplakiaoral potentially malignant disordersepi-thelial dysplasiaoral squamous cell carcinomabioinformatics analysisclinical cohort studyanimal model
《口腔疾病防治》 2026 (3)
237-245,9
国家自然科学基金项目(82472686)四川大学华西口腔医院探索与研发项目资助(RD-03-202505) This study was supported by the grants from National Natural Science Foundation of China(No.82472686)the Explora-tion and Development Project of West China Hospital of Stomatology,Sichuan University(No.RD-03-202505).
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