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Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
Identification of cisplatin-resistance related genes in head and neck squamous cell carcinoma
Yukio Yamano1, Katsuhiro Uzawa, Kengo Saito
1Department of Clinical Molecular Biology, Chiba University, Japan.
Abstract:
Resistance to cisplatin is a major obstacle to successful treatment of head and neck squamous cell carcinoma (HNSCC). To investigate the molecular mechanism of this resistance, we compared the gene expression profiles between the cisplatin-sensitive SCC cell lines (Sa-3, H-1 and KB) and the cisplatin-resistant cell lines established from them (Sa-3R, H-1R and KB-R) using Affymetrix U133 Plus 2.0 microarray. We identified 199 genes differentially expressed in each group. To identify important functional networks and ontologies to cisplatin resistance, the 199 genes were analyzed using the Ingenuity Pathway Analysis Tool. Fifty-one of these genes were mapped to genetic networks, and we validated the top-10 upregulated genes by real-time reverse transcriptase-polymerase chain reaction. Five novel genes, LUM, PDE3B, PDGF-C, NRG1 and PKD2, showed excellent concordance with the microarray data. In 48 patients with oral SCC (OSCC), positive immunohistochemical staining for the five genes correlated with chemoresistance to cisplatin-based combination chemotherapy. In addition, the expression of the five genes predicted the patient outcomes with chemotherapy. Furthermore, siRNA-directed suppressed expression of the five genes resulted in enhanced susceptibility to cisplatin-mediated apoptosis. These results suggested that these five novel genes have great potential for predicting the efficacy of cisplatin-based chemotherapy against OSCC. Global gene analysis of cisplatin-resistant cell lines may provide new insights into the mechanisms underlying clinical cisplatin resistance and improve the efficacy of chemotherapy for human HNSCC.
Insights
Five novel genes (LUM, PDE3B, PDGF-C, NRG1, PKD2) predict cisplatin resistance in head and neck squamous cell carcinoma (HNSCC). Their suppression enhances cancer cell sensitivity to chemotherapy, offering new therapeutic strategies for HNSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cisplatin resistance is a significant challenge in treating head and neck squamous cell carcinoma (HNSCC).
- Understanding the molecular mechanisms of cisplatin resistance is crucial for improving treatment efficacy.
Purpose of the Study:
- To identify novel genes associated with cisplatin resistance in HNSCC.
- To investigate the potential of these genes as biomarkers for predicting chemotherapy response and patient outcomes.
Main Methods:
- Gene expression profiling using microarrays to compare sensitive and resistant HNSCC cell lines.
- Bioinformatic analysis (Ingenuity Pathway Analysis) to identify functional gene networks.
- Validation of top upregulated genes using real-time reverse transcriptase-polymerase chain reaction (RT-PCR).
- Immunohistochemical staining in patient samples to correlate gene expression with clinical chemoresistance.
- siRNA-mediated gene silencing to assess the impact on cisplatin sensitivity and apoptosis.
Main Results:
- 199 differentially expressed genes were identified between sensitive and resistant cell lines.
- Five novel genes (LUM, PDE3B, PDGF-C, NRG1, PKD2) were validated and showed strong correlation with microarray data.
- Positive immunohistochemical staining for these five genes in oral squamous cell carcinoma (OSCC) patients correlated with cisplatin chemoresistance.
- Expression levels of the five genes predicted patient outcomes in chemotherapy.
- Suppression of these five genes via siRNA enhanced HNSCC cell susceptibility to cisplatin-induced apoptosis.
Conclusions:
- The five novel genes (LUM, PDE3B, PDGF-C, NRG1, PKD2) are potential biomarkers for predicting cisplatin efficacy in OSCC.
- Targeting these genes may offer new therapeutic strategies to overcome cisplatin resistance in HNSCC.
- Global gene expression analysis provides valuable insights into the mechanisms of clinical cisplatin resistance.
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