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Expression, Mutation, and Amplification Status of EGFR and Its Correlation with Five miRNAs in Salivary Gland Tumours
Emanuela Boštjančič1, Nina Hauptman1, Aleš Grošelj2
1Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Zaloška Cesta 4, 1000 Ljubljana, Slovenia.
Abstract:
Malignant salivary gland tumours are rare histologically and clinically heterogeneous group of tumours, missing prognostic factors and therapeutic targets. MicroRNAs (miRNAs), small noncoding RNAs, and posttranscriptional regulators of mRNA are poorly described in different subtypes of salivary gland tumours. Epidermal growth factor receptor (EGFR), an important therapeutic target and target of certain miRNAs (i.e., miR-133b), shows variable degrees of expression in salivary gland tumours. Our study included 70 parotid gland tumours of different histological subtypes. Expression, mutations, and copy number variations (CNVs) of EGFR were determined using immunohistochemistry, single-stranded conformation polymorphism, quantitative polymerase chain reaction (qPCR), and fluorescence in situ hybridization. Expression of miR-99b, miR-133b, miR-140, miR-140-3p, and let-7a was analysed using qPCR. Expression of EGFR was observed in 37% of tumours with low and 40% of tumours with high malignant potential. There were no mutations, with the majority of samples showing polysomy of chromosome 7. Based on histological subtypes, we found differential expression of all five miRNAs. We confirmed association of reactivity of EGFR, miR-133b, miR-140, miR-140-3p, and let-7a with CNV of EGFR and a positive association between miR-133b/let-7a and reactivity of EGFR. Age and need for postoperative radiotherapy were characterized as significant in multivariate survival analysis.
Insights
MicroRNAs (miRNAs) and epidermal growth factor receptor (EGFR) expression vary in salivary gland tumors. miRNA expression correlates with EGFR copy number variations and reactivity, impacting patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Malignant salivary gland tumors are rare, heterogeneous, and lack defined prognostic factors or therapeutic targets.
- MicroRNAs (miRNAs) roles in salivary gland tumors are understudied.
- Epidermal growth factor receptor (EGFR) is a potential therapeutic target with variable expression in these tumors.
Purpose of the Study:
- To investigate the expression and potential roles of specific miRNAs and EGFR in different parotid gland tumor subtypes.
- To explore the relationship between miRNA expression, EGFR alterations (mutations, CNVs), and tumor behavior.
- To identify potential prognostic factors for salivary gland tumors.
Main Methods:
- Analysis of 70 parotid gland tumors using immunohistochemistry, single-stranded conformation polymorphism, qPCR, and fluorescence in situ hybridization.
- Quantification of EGFR expression, mutations, and copy number variations (CNVs).
- Analysis of five specific miRNAs (miR-99b, miR-133b, miR-140, miR-140-3p, let-7a) expression using qPCR.
Main Results:
- EGFR expression was detected in 37% of low and 40% of high malignant potential tumors.
- No EGFR mutations were found; most samples exhibited chromosome 7 polysomy.
- Differential expression of all five miRNAs was observed across histological subtypes, with associations between miRNA expression, EGFR CNV, and EGFR reactivity.
Conclusions:
- MiRNA expression patterns and EGFR alterations are linked in salivary gland tumors.
- EGFR reactivity is positively associated with miR-133b and let-7a expression.
- Patient age and the need for postoperative radiotherapy are significant prognostic indicators.
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