Genomic Analysis Identifies TJP3 as a Prognostic Marker for Radiotherapy and Chemoradiotherapy in Oral Squamous Cell Carcinoma

Researchers from Seoul National University have conducted a study to analyze the genomic mutations and differentially expressed genes in primary oral squamous cell carcinoma (OSCC) tumors to identify prognostic markers for radiotherapy (RT) and concurrent chemo-radiation therapy (CCRT). The study used longitudinal whole-exome sequencing (WES) data from a patient who developed radiation-induced sarcoma (RIS) after CCRT, along with public datasets (TCGA and GSE41613), to identify genes associated with 24-month overall survival (OS). The results of the study identified 22 prognostic genes, which were further validated using Cox regression for OS. The study found that CLTCL1, RGL3, and H3C12 showed significant prognostic value in multivariate Cox analyses for patients with poor outcomes within 24 months post-RT, while SLC35G5, GARS1, and JPH3 were identified as prognostic markers for CCRT. The study also observed limited overlap between RT and CCRT-related genes, with TJP3 being the only common gene between the two therapies.

Key Takeaways:

  • The study analyzed somatic mutations and differentially expressed genes in primary OSCC tumors to identify prognostic markers for RT and CCRT.
  • Twenty-two prognostic genes were identified and validated using Cox regression for OS, with CLTCL1, RGL3, and H3C12 showing significant prognostic value for patients with poor outcomes within 24 months post-RT.
  • SLC35G5, GARS1, and JPH3 were identified as prognostic markers for CCRT, while TJP3 was the only common gene between RT and CCRT.
  • The study found that RT-related genes were predominantly found in primary tumors, whereas CCRT-related genes were distributed across primary tumor, inflamed granulation tissue, inflammatory myofibroblastic proliferation, and RIS.
  • The findings provide insights into molecular mechanisms underlying RT and CCRT resistance, supporting future directions in precision medicine.

Statistics:

  • The study analyzed longitudinal WES data from a patient who developed RIS after CCRT.
  • The study used Cox regression for OS, which identified 22 prognostic genes.
  • CLTCL1, RGL3, and H3C12 showed significant prognostic value in multivariate Cox analyses for patients with poor outcomes within 24 months post-RT (p-value < 0.05).
  • SLC35G5, GARS1, and JPH3 were identified as prognostic markers for CCRT (p-value < 0.05).
  • TJP3 exhibited significantly altered expression between radiosensitive and radioresistant cell lines (p = 0.037).

Sources:

  • Genomic analysis identifies TJP3 as a prognostic marker for radiotherapy and chemoradiotherapy in oral squamous cell carcinoma. Scientific Reports, 2025,15(1):1-15.
  • TCGA and GSE41613 datasets were used in the study.
  • Seoul National University and the authors' divisions are credited in the study.