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通过唾液微生物组和基因表达分析鉴定口腔鳞状细胞癌的非侵入性诊断标志物

Identification of Non-Invasive Diagnostic Markers for Oral Squamous Cell Carcinoma Through Salivary Microbiome and Gene Expression Analysis.

作者信息

Hishida Mitsuhiro, Nomoto Kosuke, Hashimoto Kengo, Ueda Sei, Nomoto Shuji

机构信息

Department of Surgery, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan.

Department of Surgery, Nagoya Central Hospital, 3-7-7 Taiko, Nakamura-ku, Nagoya 453-0801, Japan.

出版信息

Int J Mol Sci. 2025 Aug 21;26(16):8104. doi: 10.3390/ijms26168104.

DOI:10.3390/ijms26168104
PMID:40869423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12386369/
Abstract

Oral squamous cell carcinoma (OSCC) is a malignancy with a poor prognosis, and early diagnosis is essential for improving patient survival and quality of life. This study aimed to develop a non-invasive screening method based on salivary gene expression and microbiome analysis. Unstimulated saliva samples were collected from patients with OSCC, patients with oral potentially malignant disorders, and healthy controls. Microbiome profiling was performed using 16S ribosomal RNA gene sequencing. The OSCC group showed a significant increase in and Bacteroidetes and a decrease in . LEfSe analysis indicated microbial changes associated with disease progression. Receiver operating characteristic analysis demonstrated high diagnostic accuracy when multiple bacterial species were combined. An increase in Fusobacteria was also associated with a higher risk of recurrence. Gene expression analysis revealed that , , , and were significantly upregulated in OSCC, as confirmed by qRT-PCR and tissue expression data. Notably, CCL20 expression positively correlated with abundance. These findings suggest that integrated analysis of the salivary microbiome and gene expression may offer a useful non-invasive approach for early OSCC detection and disease monitoring. Furthermore, we integrated current evidence from the literature to provide a comprehensive overview.

摘要

口腔鳞状细胞癌(OSCC)是一种预后较差的恶性肿瘤,早期诊断对于提高患者生存率和生活质量至关重要。本研究旨在开发一种基于唾液基因表达和微生物组分析的非侵入性筛查方法。从OSCC患者、口腔潜在恶性疾病患者和健康对照者中收集未刺激的唾液样本。使用16S核糖体RNA基因测序进行微生物组分析。OSCC组中拟杆菌门显著增加,而 减少。线性判别分析效应大小(LEfSe)分析表明微生物变化与疾病进展相关。受试者工作特征分析表明,多种细菌物种联合使用时具有较高的诊断准确性。梭杆菌属增加也与较高的复发风险相关。基因表达分析显示,在OSCC中, 、 、 和 显著上调,定量逆转录聚合酶链反应(qRT-PCR)和组织表达数据证实了这一点。值得注意的是,CCL20表达与 丰度呈正相关。这些发现表明,唾液微生物组和基因表达的综合分析可能为早期OSCC检测和疾病监测提供一种有用的非侵入性方法。此外,我们整合了文献中的现有证据以提供全面概述。

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本文引用的文献

1
Identification of novel biomarkers involved in oral squamous cell carcinoma by whole transcriptome sequencing and bioinformatics analysis.通过全转录组测序和生物信息学分析鉴定口腔鳞状细胞癌中涉及的新型生物标志物。
Cancer Cell Int. 2025 Jul 22;25(1):277. doi: 10.1186/s12935-025-03913-9.
2
Activation of the tumor cell-intrinsic STING pathway induced by Fusobacterium nucleatum is associated with poor prognosis in esophageal cancer patients.具核梭杆菌诱导的肿瘤细胞内源性STING通路激活与食管癌患者的不良预后相关。
Esophagus. 2025 Apr;22(2):239-249. doi: 10.1007/s10388-025-01112-z. Epub 2025 Feb 14.
3
Systematic analyses uncover robust salivary microbial signatures and host-microbiome perturbations in oral squamous cell carcinoma.系统分析揭示了口腔鳞状细胞癌中强大的唾液微生物特征和宿主-微生物组扰动。
mSystems. 2025 Feb 18;10(2):e0124724. doi: 10.1128/msystems.01247-24. Epub 2025 Jan 28.
4
Integration of host gene regulation and oral microbiome reveals the influences of smoking during the development of oral squamous cell carcinoma.宿主基因调控与口腔微生物群的整合揭示了吸烟在口腔鳞状细胞癌发生发展过程中的影响。
Front Oncol. 2024 Oct 15;14:1409623. doi: 10.3389/fonc.2024.1409623. eCollection 2024.
5
The oral-gut microbiome axis in inflammatory bowel disease: from inside to insight.炎症性肠病中的口-肠道微生物轴:从内部到深入了解。
Front Immunol. 2024 Jul 26;15:1430001. doi: 10.3389/fimmu.2024.1430001. eCollection 2024.
6
Assessing the influence of sleep and sampling time on metabolites in oral fluid: implications for metabolomics studies.评估睡眠和采样时间对口腔液代谢物的影响:对代谢组学研究的启示。
Metabolomics. 2024 Aug 7;20(5):97. doi: 10.1007/s11306-024-02158-3.
7
Relationship between oral microbiota and colorectal cancer: A systematic review.口腔微生物群与结直肠癌的关系:一项系统综述。
J Periodontal Res. 2024 Dec;59(6):1071-1082. doi: 10.1111/jre.13289. Epub 2024 May 22.
8
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