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Updated: Jul 10, 2026
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Identification of molecular targets in head and neck squamous cell carcinomas based on genome-wide gene expression
Satoya Shimizu1, Naohiko Seki, Takashi Sugimoto
1Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Abstract:
DNA amplifications activate oncogenes and are hallmarks of nearly all advanced cancers including head and neck squamous cell carcinoma (HNSCC). Some oncogenes show both DNA copy number gain and mRNA overexpression. Chromosomal comparative genomic hybridization and oligonucleotide microarrays were used to examine 8 HNSCC cell lines and a plot of gene expression levels relative to their position on the chromosome was produced. Three highly up-regulated genes, NT5C3, ANLN and INHBA, were identified on chromosome 7p14. These genes were subjected to quantitative real-time RT-PCR on cDNA and genomic DNA derived from 8 HNSCC cell lines. ANLN and INHBA showed a strong positive correlation between mRNA expression and genomic DNA levels and a similar relationship was shown for the known oncogene, EGFR, at 7p11.2. In clinical samples, ANLN and INHBA showed a significantly higher expression in tumors than in normal tissues. Patients with high expression levels of INHBA had a shorter disease-free survival rate. Therefore, INHBA may be a promising prognostic marker of HNSCC.
Insights
DNA amplifications drive cancer, including head and neck squamous cell carcinoma (HNSCC). Researchers identified ANLN and INHBA genes on chromosome 7p14 that correlate with cancer progression and may serve as prognostic markers in HNSCC.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- DNA amplifications activating oncogenes are characteristic of advanced cancers, including head and neck squamous cell carcinoma (HNSCC).
- Some oncogenes exhibit both DNA copy number gains and messenger RNA (mRNA) overexpression, suggesting a link between genomic alterations and gene expression in cancer development.
Purpose of the Study:
- To identify genes on chromosome 7p that are amplified and overexpressed in HNSCC.
- To investigate the correlation between gene expression and DNA copy number for candidate genes in HNSCC cell lines.
- To evaluate the potential of identified genes as prognostic markers in HNSCC patients.
Main Methods:
- Utilized chromosomal comparative genomic hybridization and oligonucleotide microarrays to analyze 8 HNSCC cell lines.
- Generated plots of gene expression levels against chromosomal position to identify candidate genes.
- Employed quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) to assess mRNA and genomic DNA levels of selected genes (NT5C3, ANLN, INHBA) in HNSCC cell lines.
Main Results:
- Identified three highly upregulated genes (NT5C3, ANLN, INHBA) on chromosome 7p14.
- Demonstrated a strong positive correlation between mRNA expression and genomic DNA levels for ANLN and INHBA, similar to the known oncogene EGFR.
- Observed significantly higher expression of ANLN and INHBA in HNSCC tumors compared to normal tissues.
- Found that high INHBA expression levels correlated with shorter disease-free survival in HNSCC patients.
Conclusions:
- ANLN and INHBA are frequently upregulated in HNSCC, with expression levels linked to gene copy number.
- INHBA shows potential as a prognostic biomarker for predicting disease-free survival in head and neck squamous cell carcinoma.
- Further research into these genes may reveal novel therapeutic targets for HNSCC.
