Keratin 18 as a cytoskeletal regulator of epithelial–mesenchymal plasticity and prognostic risk in oral squamous cell carcinoma

Authors

• Tuan-Yu Kao, Department of Oral and Maxillofacial Surgery, National Taiwan University Hospital, Taipei, Taiwan.
• Hsuan-Chao Lin, Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
• Chien-Wei Lai, Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University College of Medicine, Taipei, Taiwan
• Julia Yu-Fong Chang, Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University College of Medicine, Taipei, Taiwan.
• Feng-Chiao Tsai, Department of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan
• Jang-Jaer Lee, Department of Oral and Maxillofacial Surgery, National Taiwan University Hospital, Taipei, Taiwan
• Jean-San Chia, Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University College of Medicine, Taipei, Taiwan.Follow

Abstract

Background/purpose: Oral squamous cell carcinoma (OSCC) shows poor survival, and conventional staging does not fully capture biologic aggressiveness. Keratin 18 (KRT18) has been linked to malignant progression in epithelial cancers, but its prognostic and biologic significance in OSCC remains unclear. This study investigated whether KRT18 expression is associated with aggressive invasion patterns and adverse outcomes in OSCC, and whether KRT18 contributes to epithelial–mesenchymal plasticity-related malignant phenotypes.

Materials and methods: Eighty-eight non-irradiated OSCC specimens obtained after primary surgical resection at National Taiwan University Hospital were analyzed by immunohistochemistry. Associations between KRT18 expression and clinicopathological variables were assessed, and survival was evaluated using Kaplan–Meier and Cox regression analyses. In SAS OSCC cells, KRT18 knockdown, rescue, and overexpression models were established for proliferation, migration, invasion, RNA sequencing, and epithelial–mesenchymal transition (EMT)-marker analyses.

Results: KRT18 expression was stronger at the invasive front than at the tumor center and correlated with worst pattern of invasion (WPOI) aggressiveness (Spearman r = 0.4799, P < 0.050). KRT18 positivity was associated with metastasis to >2 lymph nodes and independently predicted poorer overall survival. In multivariate analysis, low and high KRT18 expression showed hazard ratios of 6.93 and 5.67, respectively. KRT18 knockdown suppressed proliferation, collective migration, invasion, and the EMT hallmark gene set (normalized enrichment score = -1.41, adjusted P = 0.037).

Conclusion: KRT18 is a histopathologic and prognostic marker of invasive, high-risk OSCC and appears to support epithelial–mesenchymal plasticity-related malignant behavior. However, forced KRT18 overexpression did not consistently enhance malignant phenotypes, indicating that its biologic effects are context-dependent.

Recommended Citation

Kao, Tuan-Yu; Lin, Hsuan-Chao; Lai, Chien-Wei; Chang, Julia Yu-Fong; Tsai, Feng-Chiao; Lee, Jang-Jaer; and Chia, Jean-San (2026) "Keratin 18 as a cytoskeletal regulator of epithelial–mesenchymal plasticity and prognostic risk in oral squamous cell carcinoma," Journal of Dental Sciences: Vol. 21: Iss. 4, Article 56.
Available at: https://jds.ads.org.tw/journal/vol21/iss4/56

Publication Date

2026

Received Date

July 08 2026

Accepted Date

July 15 2026

Final Revision Date

July 14 2026