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Published on: July 22, 2020
Identification of novel biomarkers involved in oral squamous cell carcinoma by whole transcriptome sequencing and
Hongliang Du1,2,3, Zhenze Wang4, Mengyi Qi5
1The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, China.
Background:
Oral squamous cell carcinoma (OSCC) is among the most common malignant tumors in the oral and maxillofacial regions, characterized by high drug resistance and poor treatment outcomes. This underscores the urgent need to identify novel biomarkers for OSCC.
Methods:
Differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) (DE-mRNAs, DE-miRNAs, and DE-lncRNAs) between primary and control groups, as well as metastatic and primary groups, were identified using whole transcriptome sequencing data. Candidate OSCC genes were derived from DE-mRNAs. Potential biomarkers were then identified using five algorithms from CytoHubba. Biomarkers were validated via univariate Cox regression and Kaplan-Meier (K-M) survival analysis. Additional analyses included subcellular localization, mutation analysis, and Gene Set Enrichment Analysis (GSEA). Key drugs for OSCC treatment were also identified. Quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry were employed to verify the expression levels of key biomarkers.
Results:
A total of 304 candidate genes were identified, with 29 potential biomarkers selected by five algorithms. ANPEP, APOB, GLP1R, and SI exhibited significant survival differences in the K-M curves, establishing them as OSCC biomarkers. These biomarkers were predominantly localized in the cytoplasm, with SI and APOB showing the highest mutation susceptibility. Enrichment analysis revealed that the 'interferon-gamma response'biological function was co-enriched by ANPEP, APOB, and SI. Furthermore, BIBW2992 (afatinib) and PF.02341066 (crizotinib) were most strongly correlated with the biomarkers, suggesting their potential as key drugs for OSCC treatment. Additionally, the findings were validated by qRT-PCR and immunohistochemical analyses, and the results were consistent with the RNA-seq data.
Conclusion:
ANPEP, APOB, GLP1R, and SI were identified as potential OSCC biomarkers, offering valuable insights for further research and therapeutic development.
Insights
Novel oral squamous cell carcinoma (OSCC) biomarkers ANPEP, APOB, GLP1R, and SI were identified. These findings offer new avenues for OSCC research and targeted therapies, addressing the need for better treatment outcomes.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Oral squamous cell carcinoma (OSCC) presents significant challenges due to drug resistance and poor treatment outcomes.
- There is a critical need for novel biomarkers to improve OSCC diagnosis and treatment strategies.
Purpose of the Study:
- To identify and validate novel diagnostic and prognostic biomarkers for OSCC.
- To explore potential therapeutic targets and drugs for OSCC treatment.
Main Methods:
- Whole transcriptome sequencing identified differentially expressed genes (mRNAs, miRNAs, lncRNAs).
- Candidate genes were analyzed using bioinformatics algorithms (CytoHubba) and validated with Cox regression and Kaplan-Meier survival analysis.
- Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry confirmed biomarker expression.
Main Results:
- Four genes (ANPEP, APOB, GLP1R, SI) were identified as significant OSCC biomarkers with prognostic value.
- These biomarkers are primarily cytoplasmic, with SI and APOB showing high mutation susceptibility.
- Enrichment analysis highlighted the 'interferon-gamma response' pathway, and potential therapeutic agents like afatinib and crizotinib were identified.
Conclusions:
- ANPEP, APOB, GLP1R, and SI represent promising biomarkers for OSCC.
- These biomarkers provide valuable insights for developing new diagnostic tools and therapeutic strategies for OSCC.
