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Updated: Jul 12, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Clinically Relevant Mutational Signatures and Prognostic Biomarkers in Taiwanese Oral Squamous Cell Carcinoma
Chan-Chi Chang1,2, Fang-Yu Tsai3, Shang-Yin Wu4
1Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Background:
Oral squamous cell carcinoma (OSCC), primarily caused by high exposure to betel quid, tobacco, and alcohol, remains a major public health burden in Taiwan. Although key mutations have been identified in OSCC, the population-specific mutational landscape and its clinical relevance remain underexplored.
Methods:
A total of 106 OSCC tumors from Taiwanese patients were subjected to targeted gene sequencing with the Oncomine Comprehensive Assay v3 platform. High-confidence exonic, nonsynonymous variants were identified from 161 cancer-related genes. The resulting mutational landscape was compared with publicly available data from The Cancer Genome Atlas. Gene- and pathway-level alterations were further correlated with clinicopathological parameters.
Results:
A total of 317 exonic, nonsynonymous variants were identified in 73 OSCC-related genes, of which 52 were classified as driver genes. In addition to commonly mutated genes (e.g., TP53, CDKN2A, NOTCH1, HRAS, and PIK3CA), PIK3R1 and MSH6 exhibited high mutation frequencies. A higher number of mutated genes per tumor was significantly correlated with poorer local-relapse-free survival (hazard ratio: 1.17, 95% CI: 1.04-1.31, p = 0.010). In the 83 advanced-stage OSCC tumors, TP53 mutation was strongly associated with positive cervical lymph nodal metastasis (p < 0.001). An inverse relationship was noted between nodal metastasis and NOTCH1, HRAS, and PIK3CA mutations, possibly due to the mutually exclusive pattern observed between TP53 and NOTCH1/HRAS mutations. Alteration of the cell cycle oncogene pathway was significantly associated with poor survival in advanced-stage OSCC patients, which was subsequently confirmed as an independent prognostic factor for disease-specific survival (hazard ratio: 3.2, 95% CI: 1.05-9.75, p = 0.040) in 89 patients with advanced-stage OSCC from The Cancer Genome Atlas.
Conclusions:
This study uniquely illustrates the mutational landscape of OSCC in Taiwanese patients, highlighting clinically relevant genomic alterations that hold promise as prognostic biomarkers and candidates for targeted intervention.
