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咀嚼烟草使用者和口腔癌患者唾液的比较蛋白质组学分析揭示了共同的生物标志物:一项病例对照观察性研究。

Comparative proteomic analysis of saliva from chewing tobacco users and oral cancer patients reveals shared biomarkers: A case control observational study.

机构信息

Canter for Applied and Translational Genomics, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates; Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.

Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; College of Pharmacy, Department of Medicinal Chemistry, University of Sharjah, United Arab Emirates.

出版信息

J Dent. 2024 Oct;149:105268. doi: 10.1016/j.jdent.2024.105268. Epub 2024 Jul 30.

DOI:10.1016/j.jdent.2024.105268
PMID:39089670
Abstract

OBJECTIVE

The aim of this study was to compare the salivary proteomic profile of smokeless tobacco users with that of non-users and oral cancer patients using Liquid Chromatography-Mass Spectrometry/ Mass Spectrometry (LC-MS/MS).

METHODS

Saliva samples from 65 participants were collected in three groups: control (25 participants), smokeless tobacco users (25 participants), and oral cancer (15 participants).

RESULTS

The analysis revealed 343 protein groups with significantly altered abundance in the saliva samples (P < 0.05). Among these, 43 out of 51 dysregulated proteins in the smokeless tobacco group were also dysregulated in the oral cancer group. Notably, Apolipoprotein A1 (ApoA1) and Pon1 were found to be significantly increased in both smokeless tobacco users and oral cancer patients (p < 0.05). Furthermore, six out of the 20 most significantly altered proteins were mitochondrial proteins, and all of these were decreased relative to controls in both smokeless tobacco users and cancer samples.

CONCLUSION

The proteomic profile of users of chewing (smokeless) tobacco (SLT) shows substantial overlap in the altered pathways and dysregulated proteins with those altered in oral cancer samples, suggesting that SLT use induces a shift toward an oncogenic state. Specifically indicated pathways included blood microparticles, platelet α-granules and protease inhibitors as well as indicators of oxidative stress and exogenous compound processing. What differentiates oral cancer samples from SLT users is enrichment of alterations related to cytoskeletal organisation and tissue remodelling.

CLINICAL SIGNIFICANCE

The findings emphasize the importance of salivary proteomic profiles because changes in certain proteins may be indicators for early oral cancer identification and risk assessment in smokeless tobacco users.

摘要

目的

本研究旨在使用液相色谱-质谱/质谱(LC-MS/MS)比较咀嚼(无烟)烟草使用者、非使用者和口腔癌患者的唾液蛋白质组图谱。

方法

从三组参与者中收集唾液样本:对照组(25 名参与者)、咀嚼烟草使用者(25 名参与者)和口腔癌患者(15 名参与者)。

结果

分析显示,唾液样本中有 343 个蛋白质组的丰度发生了显著改变(P<0.05)。其中,咀嚼烟草组中有 51 个失调蛋白中的 43 个在口腔癌组中也失调。值得注意的是,载脂蛋白 A1(ApoA1)和 Pon1 在咀嚼烟草使用者和口腔癌患者中均显著增加(p<0.05)。此外,20 个变化最显著的蛋白质中有 6 个是线粒体蛋白,在咀嚼烟草使用者和癌症样本中,与对照组相比,这些蛋白均减少。

结论

咀嚼(无烟)烟草使用者的蛋白质组图谱显示,改变的途径和失调的蛋白与口腔癌样本中改变的途径和失调的蛋白有很大的重叠,这表明咀嚼烟草使用会导致向致癌状态转变。具体指出的途径包括血液微颗粒、血小板α-颗粒和蛋白酶抑制剂以及氧化应激和外源化合物处理的指标。使口腔癌样本与咀嚼烟草使用者区分开来的是与细胞骨架组织和组织重塑相关的改变的富集。

临床意义

这些发现强调了唾液蛋白质组图谱的重要性,因为某些蛋白质的变化可能是识别早期口腔癌和评估咀嚼烟草使用者风险的指标。

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