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唾液凋亡微泡作为预后不愈合口腔溃疡和口腔癌生物标志物的横断面研究

Salivary apoptotic microvesicles as biomarkers for prognostic non-healing oral ulcers and oral cancer: a cross-sectional study.

作者信息

Zhao Jian, Dong Yu, Shi Shuya, Yu Hongqiang, Tan Luanjun

机构信息

Department of Stomatology, the Affiliated Hospital of JiangNan University, Wuxi, 214122, Jiangsu, China.

Department of Stomatology, Shanghai East Hospital Affiliated to Tongji University, No. 150 Jimo Road, Pudong New Area, Shanghai, 200120, China.

出版信息

Sci Rep. 2025 Mar 18;15(1):9297. doi: 10.1038/s41598-025-93075-5.

DOI:10.1038/s41598-025-93075-5
PMID:40102607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11920502/
Abstract

Microvesicles (MVs) are membrane vesicles secreted by cells and are present in the saliva of healthy individuals. It has various functions and has been reported to be a biomarker for malignant tumors. The changes in saliva levels of MVs associated with disease(s) is unclear. This study aimed to determine the proportion of salivary apoptotic MVs and their association with oral ulcer(s) in patients with non-healing oral ulcer(s) and reported oral cancer. Saliva (5 mL) was collected from patients with non-healing oral ulcer(s) and reported oral cancer (at the time of saliva collection, the participant have an oral ulcer(s) in the oral cavity and have an oral cancer lesion; n = 73) and healthy volunteers with oral ulcer(s) (n = 62). A standard differential centrifugation protocol was used for the purification of MVs. Dynamic light scattering and transmission electron microscopy were used to characterize MVs. Flow cytometry was used to quantify salivary apoptotic MVs. Immunocytochemistry was performed according to a standard protocol. None of patients with oral cancer has smoking and drinking habit. The majority of saliva samples derived from patients with non-healing oral ulcer(s) and reported oral cancer were more positive for the fluorescent dye carboxyfluorescein succinimidyl ester than those of healthy volunteers with oral ulcer(s). Salivary fluid obtained from patients had membrane-limited vesicles that were round and/or slightly elongated in shape, with diameters of 100-1,000 nm. The number of salivary apoptotic MVs was higher in patients with non-healing oral ulcer(s) than in those derived from healthy volunteers with oral ulcer(s) (p < 0.001). There was an association between salivary apoptotic MVs in patients with non-healing oral ulcer(s) and the degree or severity of oral ulcers (p < 0.001). Levels of salivary apoptotic MVs are elevated in patients with non-healing oral ulcer(s) and confirmed oral cancer. Elevated levels of salivary apoptotic MVs are associated with clinicopathological data of patients with oral cancer. Evidence level: IV. Technical efficacy: stage 3.

摘要

微泡(MVs)是细胞分泌的膜泡,存在于健康个体的唾液中。它具有多种功能,据报道是恶性肿瘤的生物标志物。与疾病相关的唾液中MVs水平的变化尚不清楚。本研究旨在确定非愈合性口腔溃疡和已报告口腔癌患者唾液中凋亡性MVs的比例及其与口腔溃疡的关系。从非愈合性口腔溃疡和已报告口腔癌患者(在采集唾液时,参与者口腔内有口腔溃疡且有口腔癌病变;n = 73)以及有口腔溃疡的健康志愿者(n = 62)中收集5毫升唾液。采用标准差速离心方案纯化MVs。使用动态光散射和透射电子显微镜对MVs进行表征。采用流式细胞术对唾液中凋亡性MVs进行定量。按照标准方案进行免疫细胞化学检测。所有口腔癌患者均无吸烟和饮酒习惯。来自非愈合性口腔溃疡和已报告口腔癌患者的大多数唾液样本对荧光染料羧基荧光素琥珀酰亚胺酯的阳性反应高于有口腔溃疡的健康志愿者。从患者获得的唾液中有膜包被的囊泡,其形状为圆形和/或略呈椭圆形,直径为100 - 1000纳米。非愈合性口腔溃疡患者唾液中凋亡性MVs的数量高于有口腔溃疡的健康志愿者(p < 0.001)。非愈合性口腔溃疡患者唾液中凋亡性MVs与口腔溃疡的程度或严重程度之间存在关联(p < 0.001)。非愈合性口腔溃疡和确诊口腔癌患者唾液中凋亡性MVs水平升高。唾液中凋亡性MVs水平升高与口腔癌患者的临床病理数据相关。证据水平:IV。技术疗效:3期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/539989243938/41598_2025_93075_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/a56db726f7b4/41598_2025_93075_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/faab107bbc26/41598_2025_93075_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/539989243938/41598_2025_93075_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/a56db726f7b4/41598_2025_93075_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/e38d8490b2fe/41598_2025_93075_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/3b40ae03e461/41598_2025_93075_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/4f70feac5c46/41598_2025_93075_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/faab107bbc26/41598_2025_93075_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f098/11920502/539989243938/41598_2025_93075_Fig6_HTML.jpg

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Comparison of Salivary and Serum Alkaline Phosphates Level and Lactate Dehydrogenase Levels in Patients with Tobacco Related Oral Lesions with Healthy Subjects - A Step Towards Early Diagnosis.比较烟草相关口腔病变患者和健康受试者的唾液和血清碱性磷酸酶水平及乳酸脱氢酶水平——迈向早期诊断的一步。
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