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Open AccessArticle
Identification of Non-Invasive Diagnostic Markers for Oral Squamous Cell Carcinoma Through Salivary Microbiome and Gene Expression Analysis
by
Mitsuhiro Hishida
Mitsuhiro Hishida
Kosuke Nomoto
Kosuke Nomoto
Kengo Hashimoto
Kengo Hashimoto 
,
Sei Ueda
Sei Ueda
Shuji Nomoto
Shuji Nomoto
1
Department of Surgery, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan
2
Department of Surgery, Nagoya Central Hospital, 3-7-7 Taiko, Nakamura-ku, Nagoya 453-0801, Japan
3
Department of Maxillofacial Surgery, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(16), 8104; https://doi.org/10.3390/ijms26168104 (registering DOI)
Submission received: 30 June 2025
/
Revised: 15 August 2025
/
Accepted: 19 August 2025
/
Published: 21 August 2025
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 Fusobacterium and Bacteroidetes and a decrease in Streptococcus. 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 NUS1, RCN1, CPLANE1, and CCL20 were significantly upregulated in OSCC, as confirmed by qRT-PCR and tissue expression data. Notably, CCL20 expression positively correlated with Fusobacterium 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.
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MDPI and ACS Style
Hishida, M.; Nomoto, K.; Hashimoto, K.; Ueda, S.; Nomoto, S.
Identification of Non-Invasive Diagnostic Markers for Oral Squamous Cell Carcinoma Through Salivary Microbiome and Gene Expression Analysis. Int. J. Mol. Sci. 2025, 26, 8104.
https://doi.org/10.3390/ijms26168104
AMA Style
Hishida M, Nomoto K, Hashimoto K, Ueda S, Nomoto S.
Identification of Non-Invasive Diagnostic Markers for Oral Squamous Cell Carcinoma Through Salivary Microbiome and Gene Expression Analysis. International Journal of Molecular Sciences. 2025; 26(16):8104.
https://doi.org/10.3390/ijms26168104
Chicago/Turabian Style
Hishida, Mitsuhiro, Kosuke Nomoto, Kengo Hashimoto, Sei Ueda, and Shuji Nomoto.
2025. "Identification of Non-Invasive Diagnostic Markers for Oral Squamous Cell Carcinoma Through Salivary Microbiome and Gene Expression Analysis" International Journal of Molecular Sciences 26, no. 16: 8104.
https://doi.org/10.3390/ijms26168104
APA Style
Hishida, M., Nomoto, K., Hashimoto, K., Ueda, S., & Nomoto, S.
(2025). Identification of Non-Invasive Diagnostic Markers for Oral Squamous Cell Carcinoma Through Salivary Microbiome and Gene Expression Analysis. International Journal of Molecular Sciences, 26(16), 8104.
https://doi.org/10.3390/ijms26168104
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