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PI3K/AKT/mTOR pathway and autophagy regulator genes in paranasal squamous cell carcinoma metastasis
Cigir Biray Avci1, Baha Sezgin2, Bakiye Goker Bagca3
1Medical Biology Department, Ege University School of Medicine, Bornova, 35100, Izmir, Turkey.
Abstract:
Although there are many studies on the role of PI3K/AKT/mTOR pathway and autophagy genes in the mechanism of head and neck cancer formation and prognostic significance, there is no study investigating the role of the genes in paranasal sinus carcinomas. The aim of the study was to assess the role of the PI3K/AKT/mTOR pathway and autophagy related gene expression changes in squamous cell carcinoma of paranasal sinuses with and without neck metastasis. Eight paranasal squamous cell carcinoma patients (five without and three with neck metastasis) were included. Tissues were obtained during the surgery. Total RNA was isolated from the tissues and cDNA synthesis was performed. Expression levels of the genes were determined using qRT-PCR method. The results were evaluated using the 2-∆∆Ct method, and fold changes of the gene expression levels in primary tumor and neck metastasis tissues were calculated according to the normal tissue. Expression levels of both PI3K/AKT/mTOR pathway and positive regulators of autophagy were significantly increased in metastasis-related two groups, especially in neck metastasis tissues. The increase in PI3K/AKT/mTOR pathway and autophagy related gene expression levels may support the metastatic character in paranasal squamous cell carcinomas. This is the first study to assess autophagy related genes in paranasal sinus cancer at transcriptome-level. Support of the transcriptome-level findings by the further protein analyses will contribute to the illumination of the rare paranasal sinus cancer molecular biology.
Insights
This study reveals that increased expression of the PI3K/AKT/mTOR pathway and autophagy genes may drive metastasis in paranasal sinus cancers. These findings offer new insights into the molecular mechanisms of this rare cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Paranasal sinus carcinomas are rare cancers with limited understanding of their molecular drivers.
- The PI3K/AKT/mTOR pathway and autophagy are implicated in head and neck cancers but not specifically studied in paranasal sinus carcinomas.
Purpose of the Study:
- To investigate the gene expression of the PI3K/AKT/mTOR pathway and autophagy in paranasal sinus squamous cell carcinoma.
- To determine if these molecular changes correlate with the presence or absence of neck metastasis.
Main Methods:
- Gene expression analysis using qRT-PCR on tissue samples from eight paranasal sinus carcinoma patients.
- Evaluation of gene expression levels using the 2-∆∆Ct method and fold change calculations.
Main Results:
- Significantly increased expression of PI3K/AKT/mTOR pathway and autophagy-related genes was observed.
- Elevated gene expression was particularly pronounced in neck metastasis tissues compared to primary tumors.
Conclusions:
- Upregulation of the PI3K/AKT/mTOR pathway and autophagy genes may contribute to the metastatic potential of paranasal sinus squamous cell carcinomas.
- This is the first transcriptome-level assessment of autophagy genes in paranasal sinus cancer, highlighting potential targets for future research.
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