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Updated: Aug 13, 2026

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
07:29

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment

Published on: April 22, 2019

SMAD4 Expression and Its Association With Treatment Resistance and Clinical Outcomes in Oral Squamous Cell Carcinoma

Junki Sakata1, Akiyuki Hirosue2, Ryoji Yoshida1

  • 1Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Cancer Reports (Hoboken, N.J.)
|August 11, 2026
PubMed
Abstract

Insights

Low SMAD4 expression in oral squamous cell carcinoma (OSCC) correlates with increased metastasis, poor response to chemoradiotherapy, and adverse prognosis. This suggests SMAD4 impacts treatment sensitivity and patient outcomes in OSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Small mothers against decapentaplegic homologue 4 (SMAD4) is crucial in transforming growth factor-beta (TGF-β) signaling and cancer development.
  • SMAD4 expression patterns and roles in oral squamous cell carcinoma (OSCC) remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the clinical and biological significance of SMAD4 expression in oral squamous cell carcinoma (OSCC).
  • To investigate the association between SMAD4 levels and patient outcomes following chemoradiotherapy and surgery.

Main Methods:

  • Immunohistochemical analysis of SMAD4 expression in 90 OSCC patient specimens.
  • Correlation analysis of SMAD4 expression with clinicopathological features.
  • In vitro studies assessing SMAD4 effects on chemosensitivity and apoptosis-related molecules.

Main Results:

  • Low SMAD4 expression significantly correlated with increased lymph node metastasis risk.
  • Reduced SMAD4 expression was linked to poor response to 5-FU-based chemoradiotherapy and adverse prognosis.
  • SMAD4 downregulation decreased OSCC cell sensitivity to cisplatin and 5-fluorouracil, increasing cIAP2 expression.

Conclusions:

  • Reduced SMAD4 expression is associated with chemotherapy resistance and poorer prognosis in OSCC.
  • SMAD4 may not serve as an independent prognostic biomarker in OSCC.
  • Further research is needed to validate these findings in a broader OSCC patient population.
Keywords:
SMAD4apoptosischemoresistanceoral squamous cell carcinomatherapeutic resistance

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